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Reviews in the Neurosciences

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Volume 25, Issue 3 (Jun 2014)


Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative

Alfredo Meneses
  • Corresponding author
  • Department of Pharmacobiology, CINVESTAV, Tenorios 235, Granjas Coapa, Mexico City 14330, Mexico
  • Email:
Published Online: 2014-04-03 | DOI: https://doi.org/10.1515/revneuro-2014-0001


Agonists and antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) or receptor7 (5-HT7) might improve memory and/or reverse amnesia, although the mechanisms involved are poorly understood. Hence, the current work summarizes recent reviews and findings involving these receptors. Evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effect in conditions, such as memory formation, age-related cognitive impairments and memory deficit in preclinical studies, as well as in diseases such as schizophrenia, Parkinson’s, and Alzheimer’s disease (AD). Memory, aging, and AD modify 5-HT6 receptors and signaling cascades; likewise, the modulation of 5-HT6 drugs on memory seems to be accompanied with neural changes. Moreover, 5-HT7 receptors are localized in brain areas mediating memory, including the cortex, hippocampus (e.g., Zola-Morgan and Squire, 1993) and raphe nuclei; however, the role of these receptors on memory has yet to be fully explored. Hence, findings and reviews are summarized in this work. Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects. These effects seem to be dependent on the basal level of performance, i.e., normal or impaired. Available evidence suggests that a potential utility of 5-HT6 and 5-HT7 receptor in mild-to-moderate AD patients and other memory dysfunctions as therapeutic targets.

Keywords: drugs; memory; 5-HT receptors


  • Adamantidis, A. and de Lecea, L. (2009). A role for melanin-concentrating hormone in learning and memory. Peptides 30, 2066–2070. [Crossref]

  • Altman, H.J. and Normile, H.J. (1988). What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia. Neurobiol. Aging 9, 627–638. [Crossref] [PubMed]

  • Aubert, Y., Allers, K.A., Sommer, B., de Kloet, ER., Abbott, D.H., and Datson, N.A. (2013). Brain region-specific transcriptomic markers of serotonin-1A receptor agonist action mediating sexual rejection and aggression in female marmoset monkeys. J. Sex. Med. 10, 1461–1475. [Crossref]

  • Ballaz, S.J., Akil, H., and Watson, S.J. (2007a). The 5-HT7 receptor: role in novel object discrimination and relation to novelty-seeking behavior. Neuroscience 149, 192–202. [Crossref]

  • Ballaz, S.J., Akil, H., and Watson S.J. (2007b). Analysis of 5-HT6 and 5-HT7 receptor gene expression in rats showing differences in novelty-seeking behavior. Neuroscience 147, 428–438. [Crossref]

  • Barbas, D., DesGroseillers, L., Castellucci, V.F., Carew, T.J., and Marinesco, S. (2003). Multiple serotonergic mechanisms contributing to sensitization in aplysia: evidence of diverse serotonin receptor subtypes. Learn Mem. 10, 373–386. [PubMed]

  • Belcher, A.M., O’Dell, S.J., and Marshall, J.F. (2005). Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity. Neuropsychopharmacology 30, 2026–2034. [Crossref]

  • Berger, M., Gray, J.A., and Roth, B.L. (2009). The expanded biology of serotonin. Annu. Rev. Med. 60, 355–366. [Crossref] [PubMed]

  • Bockaert, J., Claeysen, S., Bécamel, C., Dumuis, A., and Marin, P. (2006). Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res. 326, 553–572.

  • Bockaert, J., Claeysen, S., Compan, V., and Dumuis, A. (2008). 5-HT4 receptors: history, molecular pharmacology and brain functions. Neuropharmacology 55, 922–931. [Crossref]

  • Bockaert, J., Claeysen, S., Compan, V., and Dumuis, A. (2011). 5-HT4 receptors, a place in the sun: act two. Curr. Opin. Pharmacol. 11, 87–93. [Crossref]

  • Bonkale, W.L., Fastbom, J., Wiehager, B., Ravid, R., Winblad, B., and Cowburn, R.F. (1996). Impaired G-protein-stimulated adenylyl cyclase activity in Alzheimer’s disease brain is not accompanied by reduced cyclic-AMP-dependent protein kinase A activity. Brain Res. 737, 155–161.

  • Bonsi, P., Cuomo, D., Ding, J., Sciamanna, G., Ulrich, S., Tscherter, A., Bernardi, G., Surmeier, D.J., and Pisani, A. (2007). Endogenous serotonin excites striatal cholinergic interneurons via the activation of 5-HT2C, 5-HT6, and 5-HT7 serotonin receptors: implications for extrapyramidal side effects of serotonin reuptake inhibitors. Neuropsychopharmacology 32, 1840–1854. [Crossref]

  • Borg, J. (2008). Molecular imaging of the 5-HT1A receptor in relation to human cognition. Behav Brain Res. 195, 103–111.

  • Bosker, F.J., Folgering, J.H., Gladkevich, A.V., Schmidt, A., van der Hart, M.C., Sprouse, J., den Boer, J.A., Westerink, B.H., and Cremers, T.I. (2009). Antagonism of 5-HT(1A) receptors uncovers an excitatory effect of SSRIs on 5-HT neuronal activity, an action probably mediated by 5-HT(7) receptors. J. Neurochem. 108, 1126–1135. [Crossref]

  • Boulougouris, V. and Robbins, T.W. (2010). Enhancement of spatial reversal learning by 5-HT2C receptor antagonism is neuroanatomically specific. J. Neurosci. 30, 930–938. [Crossref]

  • Bourson, A., Borroni, E., Austin, R.H., Monsma, F.J. Jr., and Sleight, A.J. (1995). Determination of the role of the 5-ht6 receptor in the rat brain: a study using antisense oligonucleotides. J. Pharmacol. Exp. Ther. 274, 173–180.

  • Branchek, T.A. and Blackburn, T.P. (2000). 5-ht6 receptors as emerging targets for drug discovery. Annu. Rev. Pharmacol. Toxicol. 40, 319–334. [Crossref]

  • Briand, L.A., Gritton, H., Howe, W.M., Young, D.A., and Sarter, M. (2007). Modulators in concert for cognition: modulator interactions in the prefrontal cortex. Prog. Neurobiol. 83, 69–91. [Crossref] [PubMed]

  • Buchhave, P., Minthon, L., Zetterberg, H., Wallin, A.K., Blennow, K., and Hansson, O. (2012). Cerebrospinal fluid levels of β-amyloid 1–42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen. Psychiatry 69, 98–106.

  • Buhot, M.C., Wolff, M., and Segu, L. (2003). Serotonin. Memories are Made of These: From Messengers to Molecules. Gernot Riedel and Bettina Platt., eds. Amsterdam: Eurekah.com and Kluwer Academic/Plenum Publishers, pp. 1–19.

  • Burnham, K.E., Baxter, M.G., Dawson, L.A., Southam, E., Sharp, T., and Bannerman, D.M. (2007). Effect of the 5-HT6 receptor agonist WAY181187 on prefrontal cortical function in the rat. Neurosci. Abstract 741, 28.AAA1.

  • Burnham, K.E., Baxter, M.G., Bainton, J.R., Southam, E., Dawson, L.A., Bannerman, D.M., and Sharp, T. (2010). Activation of 5-HT6 receptors facilitates attentional set shifting. Psychopharmacol (Berl.) 208, 13–21.

  • Bussey, T.J., Holmes, A., Lyon, L., Mar, A.C., McAllister, K.A., Nithianantharajah, J., Oomen, C.A., and Saksida, L.M. (2012). New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology 62, 1191–1203. [PubMed] [Crossref]

  • Cadogan, A.K., Kendall, D.A., and Marsden, C.A. (1994). Serotonin 5-HT1A receptor activation increases cyclic AMP formation in the rat hippocampus in vivo. J. Neurochem. 62, 1816–1821.

  • Calcagno, E., Carli, M., and Invernizzi, R.W. (2006). The 5-HT1A receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors. J. Neurochem. 96, 853–860. [Crossref]

  • Callaghan, C.K., Hok, V., Della-Chiesa, A., Virley, D.J., Upton, N., and O’Mara, S.M. (2012). Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457. Neuropharmacol. 63, 890–897. [Crossref]

  • Callaghan, B.L., Li, S., and Richardson, R. (2014). The elusive engram: what can infantile amnesia tell us about memory? Trends Neurosci. 37, 47–53. [PubMed] [Crossref]

  • Cammarota, M., Bevilaqua, L.R., Medina, J.H., and Izquierdo, I. (2008). ERK1/2 and CaMKII-mediated events in memory formation: is 5HT regulation involved? Behav. Brain Res. 195, 120–128.

  • Cassel, J.C. (2010). Experimental studies on the role(s) of serotonin in learning and memory functions. Handbook of the Behavioral Neurobiology of Serotonin. C.P. Müller and B.L. Jacobs, eds. Vol. 21. (Amsterdam: Academic Press), pp. 429–447.

  • Chang, S.D., and Liang, K.C. (2012). Roles of hippocampal GABAA and muscarinic receptors in consolidation of context memory and context-shock association in contextual fear conditioning: a double dissociation study. Neurobiol. Learn Mem. 98, 17–24. [Crossref] [PubMed]

  • Charnay, Y., and Léger, L. (2010). Brain serotonergic circuitries. Dialogues Clin. Neurosci. 12, 471–487. [PubMed]

  • Choi, Y.H., Kang, H., Lee, W.K., Kim, T., Rhim, H., and Yu, Y.G. (2007). An inhibitory compound against the interaction between G alpha(s) and the third intracellular loop region of serotonin receptor subtype 6 (5-HT6) disrupts the signaling pathway of 5-HT6. Exp. Mol. Med. 39, 335–342. [Crossref]

  • Chou, Y.H., Wang, S.J., Lirng, J.F., Lin, C.L., Yang, K.C., Chen, C.K., Yeh, C.B., and Liao, M.H. (2012). Impaired cognition in bipolar I disorder: the roles of the serotonin transporter and brain-derived neurotrophic factor. J. Affect. Disord. 143, 131–137. [Crossref]

  • Cifariello, A., Pompili, A., and Gasbarri, A. (2008). 5-HT7 receptors in the modulation of cognitive processes. Behav. Brain Res. 195 171–179.

  • Ciranna, L. (2006). Serotonin as a modulator of glutamate- and GABA-mediated neurotransmission: implications in physiological functions and in pathology. Curr. Neuropharmacol. 4, 101–114. [PubMed] [Crossref]

  • Clifford R.J., Holtzman, D.M. (2013). Biomarker modeling of Alzheimer’s Disease. Neuron. 80, 1347–1358.

  • Cochet, M., Donneger, R., Cassier, E., Gaven, F., Lichtenthaler, S.F., Marin, P., Bockaert, J., and Claeysen, S. (2013). 5HT4 receptors constitutively promote the non-Amyloidogenic pathway of APP cleavage and interact with ADAM10. ACS Chemical Neurosci. 4, 130−140.

  • Codony, X., Burgueño, J., Ramírez, M.J., and Vela, J.M. (2010). 5-HT6 receptor signal transduction second messenger systems. Int. Rev. Neurobiol. 94, 89–110. [Crossref]

  • Codony, X., Vela, J.M., and Ramírez, M.J. (2011). 5-HT6 receptor and cognition. Curr. Opin. Pharmacol. 11, 94–100. [Crossref]

  • Cook, R.G., Geller, A.I., Zhang, G.R., and Gowda, R. (2004). Touchscreen-enhanced visual learning in rats. Behav. Res. Met. Instrum. Comput. 36, 101–106. [Crossref]

  • Costa, L., Spatuzza, M., D’Antoni, S., Bonaccorso, C.M., Trovato, C., Musumeci, S.A., Leopoldo, M., Lacivita, E., Catania, M.V., and Ciranna, L. (2012). Activation of 5-HT7 serotonin receptors reverses metabotropic glutamate receptor-mediated synaptic plasticity in wild-type and Fmr1 knockout mice, a model of Fragile X syndrome. Biol. Psychiatry 72, 924–933. [Crossref]

  • Da Silva Costa-Aze, V., Dauphin, F., and Boulouard, M. (2011). Serotonin 5-HT6 receptor blockade reverses the age-related deficits of recognition memory and working memory in mice. Behav. Brain Res. 222, 134–140.

  • Da Silva Costa-Aze, V., Quiedeville, A., Boulouard, M., and Dauphin F. (2012). 5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice. Psychopharmacology (Berl.) 222, 99–115.

  • Davis, H.P. and Squire, L. (1984). The pharmacology of memory: a review. Psychol. Bull. 96, 518–559. [Crossref] [PubMed]

  • Dawson, L.A. (2011). The central role of 5-HT6 receptors in modulating brain neurochemistry. Int. Rev. Neurobiol. 96, 1–26. [Crossref]

  • Dawson, L.A., Nguyen, H.Q., and Li, P. (2001). The 5-HT6 receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology 25, 662–668. [Crossref]

  • Dayan, P. and Huys, Q.J. (2009). Serotonin in affective control. Ann. Rev. Neurosci. 32, 95–126. [Crossref]

  • de Foubert, G., O’Neill, M.J., and Zetterström, T.S. (2007). Acute onset by 5-HT6-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression. Neurosci. 147, 778–785. [Crossref]

  • Dijk, S.N., Francis, P.T., Stratmann, G.C., and Bowen, D.M. (1995). NMDA-induced glutamate and aspartate release from rat cortical pyramidal neurones: evidence for modulation by a 5-HT1A antagonist. Br. J. Pharmacol. 115, 1169–1174.

  • Drago, A., Alboni, S., Brunello, N., De Ronchi, D., and Serretti, A. (2010). HTR1B as a risk profile maker in psychiatric disorders: a review through motivation and memory. Eur. J. Clin. Pharmacol. 66, 5–27. doi: 10.1007/s00228-009-0724-6. Epub 2009 Oct 7. Review. Erratum in: Eur. J. Clin. Pharmacol. 66:105. [Crossref]

  • Eichenbaum, H. (2013). What H.M. taught us. J. Cogn. Neurosci. 25, 14–21.

  • Elvander-Tottie, E., Eriksson, T.M., Sandin J., and Ogren, S.O. (2009). 5-HT1A and NMDA receptors interact in the rat medial septum and modulate hippocampal-dependent spatial learning. Hippocampus 19, 1187–1198. [Crossref]

  • Engelborghs, S., Sleegers, K., Van der Mussele, S., Le Bastard, N., Brouwers, N., Van Broeckhoven, C., and De Deyn, P.P. (2013). Brain-specific tryptophan hydroxylase, TPH2, and 5-HTTLPR are associated with frontal lobe symptoms in Alzheimer’s disease. J. Alzheimers Dis. 35, 67–73.

  • Eppinger, B., Hämmerer, D., and Li, S.C. (2012). Neuromodulation of reward-based learning and decision making in human aging. Ann. NY Acad. Sci. 1235, 1–17.

  • Eriksson, T.M., Holst, S., Stan, T.L., Hager, T., Sjögren, B., Ogren, S.O., Svenningsson, P., and Stiedl, O. (2012). 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors. Neuropharmacology 63, 1150–1160. [Crossref]

  • Fink, K.B. and Göthert, M. (2007). 5-HT receptor regulation of neurotransmitter release. Pharmacol. Rev. 59, 360–417. [Crossref]

  • Fischer, A., Sananbenesi, F., Spiess, J., and Radulovic, J. (2003). Cdk5: a novel role in learning and memory. Neurosignals 12, 200–208. [Crossref]

  • Fishell, G. and Heintz, N. (2013). The neuron identity problem, form meets function. Neuron 80, 602–612. [PubMed] [Crossref]

  • Fitzpatrick, C.J., Gopalakrishnan, S., Cogan, E.S., Yager, L.M., Meyer, P.J., Lovic., V., Saunders, B.T., Parker, C.C., Gonzales, N.M., Aryee, E., et al. (2013). Variation in the form of pavlovian conditioned approach behavior among outbred male sprague-dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking. PLoS One 8, e75042.

  • Flagel, S.B., Waselus, M., Clinton, S.M., Watson, S.J., and Akil, H. (2014). Antecedents and consequences of drug abuse in rats selectively bred for high and low response to novelty. Neuropharmacology 76, Part B, 425–436. [PubMed] [Crossref]

  • Foley, A.G., Murphy, K.J., Hirst, W.D., Gallagher, H.C., Hagan, J.J., Upton, N., Walsh, F.S., and Regan, C.M. (2004). The 5-HT6 receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of an inhibitory avoidance task and ameliorates spatial task deficits in aged rats. Neuropsychopharmacology 29, 93–100. [Crossref]

  • Fone, K.C. (2006). Selective 5-HT6 compounds as a novel approach to the treatment of Alzheimer disease. J. Pharmacol. Sci. 101(Suppl 1), 53.

  • Fone, K.C. (2008). An update on the role of the 5-hydroxytryptamine6 receptor in cognitive function. Neuropharmacology 55, 1015–1022. [Crossref]

  • Fone, K.C.F., Watson, D.J.G., Khan, A., Marin, P., Bockaert, J., and Millan M. (2012). Functional role of 5HT6 receptor in the neuro-developmental cognitive deficits seen in schizophrenia. Serotonin Club meeting, Abstract pp, 59. July 10–12, 2012, Montpellier, France.

  • Fournet, V., de Lavilléon, G., Schweitzer, A., Giros, B., Andrieux, A., and Martres, M.P. (2012). Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood-status of STOP/MAP6 KO mice. J. Neurochem. 123, 982–96. [Crossref]

  • Frankland, P., Köhler, S., and Josselyn, S.A. (2013). Hippocampal neurogenesis and forgetting. Trends Neurosci. 36, 497–503. [Crossref] [PubMed]

  • Freret, T., Paizanis, E., Beaudet, G., Gusmao-Montaigne, A., Nee, G., Dauphin, F., Bouet, V., and Boulouard, M. (2014). Modulation of 5-HT7 receptor, effect on object recognition performances in mice. Psychopharmacology (Berl.) 231, 393–400.

  • Freunberger, R., Werkle-Bergner, M., Griesmayr, B., Lindenberger, U., and Klimesch, W. (2011). Brain oscillatory correlates of working memory constraints. Brain Res. 1375, 93–102.

  • Gacsályi, I., Nagy, K., Pallagi, K., Lévay, G., Hársing, L.G Jr., Móricz, K., Kertész, S., Varga, P., Haller, J., Gigler, G., et al. (2013). Egis-11150: a candidate antipsychotic compound with procognitive efficacy in rodents. Neuropharmacology 64, 254–263. [Crossref]

  • Garcia-Alloza, M., Hirst, W.D., Chen, C.P., Lasheras, B., Francis, P.T. and Ramírez, M.J. (2004). Differential involvement of 5-HT1B/1D and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer’s disease. Neuropsychopharmacol. 29, 410–416. [Crossref]

  • Geldenhuys, W.J. and Van der Schyf, C.J. (2008). 5-HT6 receptor antagonists for the treatment of Alzheimer’s disease. Curr. Top Med. Chem. 8, 1035–1048. [Crossref]

  • Geldenhuys, W.J. and Van der Schyf, C.J. (2009). The serotonin 5-HT6 receptor, a viable drug target for treating cognitive deficits in Alzheimer’s disease. Expert Rev. Neurother. 9, 1073–1085. [Crossref]

  • Geldenhuys, W.J. and Van der Schyf, C.J. (2011). Role of serotonin in Alzheimer’s disease, a new therapeutic target? CNS Drugs 25, 765–781. [Crossref]

  • Gellynck, E., Heyninck, K., Andressen, K.W., Haegeman, G., Levy, F.O., Vanhoenacker, P., and Van Craenenbroeck, K. (2013). The serotonin 5-HT7 receptors: two decades of research. Exp. Brain Res. 230, 555–568.

  • Gérard, C., El Mestikawy, S., Lebrand, C., Adrien, J., Ruat, M., Traiffort, E., Hamon, M., and Martres, M.P. (1996). Quantitative RT-PCR distribution of serotonin 5-HT6 receptor mRNA in the central nervous system of control or 5,7-dihydroxitriptamine-treated rats. Synapse 23, 164–173.

  • Gérard, C., Martres, M.P., Lefevre, K., Miquel, M.C., Verge, D., Lanfumey, L., Doucet, E., Hamon, M., and El Mestikawy, S. (1997). Inmuno-localization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res. 746, 207–19.

  • Goghari, V.M., Smith, G.N., Honer, W.G., Kopala, L.C., Thornton, A.E., Su, W., Macewan, G.W., and Lang, D.J. (2013). Effects of eight weeks of atypical antipsychotic treatment on middle frontal thickness in drug-naïve first-episode psychosis patients. Schizophr Res. 149, 149–155. [PubMed]

  • Gong, P., Zheng, Z., Chi, W., Lei, X., Wu, X., Chen, D., Zhang, K., Zheng, A., Gao, X., and Zhang, F. (2012). An association study of the genetic polymorphisms in 13 neural plasticity-related genes with semantic and episodic memories. J. Mol. Neurosci. 46, 352–361. [Crossref]

  • Gonzalez, R., Chávez-Pascacio, K., and Meneses, A. (2013). Role of 5-HT5A receptors in the consolidation of memory. Behav. Brain Res. 252, 246–251. [Crossref]

  • Grandoch, M., Roscioni, S.S., and Schmidt, M. (2010). The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function. Br. J. Pharmacol. 159, 265–284.

  • Gravius, A., Laszy, J., Pietraszek, M., Sághy, K., Nagel, J., Chambon, C., Wegener, N., Valastro, B., Danysz, W., and Gyertyán, I. (2011). Effects of 5-HT6 antagonists, Ro-4368554 and SB-258585, in tests used for the detection of cognitive enhancement and antipsychotic-like activity. Behav. Pharmacol. 22, 122–135. [Crossref]

  • Haahr, M.E., Fisher, P., Holst, K., Madsen, K., Jensen, C.G., Marner, L., Lehel, S., Baaré, W., Knudsen, G., and Hasselbalch, S. (2012). The 5-HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans. Hum. Brain Mapp. doi: 10.1002/hbm.22123. [Epub ahead of print]. [Crossref]

  • Haider, S., Khaliq, S., Tabassum, S., and Haleem, D.J. (2012). Role of somatodendritic and postsynaptic 5-HT1A receptors on learning and memory functions in rats. Neurochem. Res. 37, 2161–2166. [Crossref]

  • Hajjo, R., Setola, V., Roth, B.L., and Tropsha, A. (2012). Chemocentric informatics approach to drug discovery: identification and experimental validation of selective estrogen receptor modulators as ligands of 5-hydroxytryptamine-6 receptors and as potential cognition enhancers. J. Med. Chem. 55, 5704–5719. [Crossref]

  • Hannon, J. and Hoyer, D. (2008). Molecular biology of 5-HT receptors. Behav. Brain Res. 195, 198–213.

  • Harsing, L.G. Jr. (2006). The pharmacology of the neurochemical transmission in the midbrain raphe nuclei of the rat. Curr. Neuropharmacol 4, 313–339. [PubMed] [Crossref]

  • Hatcher, P.D., Brown, V.J., Tait, D.S., Bate, S., Overend, P., Hagan, J.J., and Jones, D.N. (2005). 5-HT6 receptor antagonists improve performance in an attentional set shifting task in rats. Psychopharmacology (Berl.) 181, 253–259.

  • Healy, D.J. and Meador-Woodruff, J.H. (1999). Ionotropic glutamate receptor modulation of 5-HT6 and 5-HT7 mRNA expression in rat brain. Neuropsychopharmacology 21, 341–351. [Crossref]

  • Hedlund, P.B., Leopoldo, M., Caccia, S., Sarkisyan, G., Fracasso, C., Martelli, G., Lacivita, E., Berardi, F. and Perrone, R. (2010). LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor. Neurosci Lett. 481, 12–16.

  • Hermann, A., Küpper, Y., Schmitz, A., Walter, B., Vaitl, D., Hennig, J., Stark, R. and Tabbert, K. (2012). Functional gene polymorphisms in the serotonin system and traumatic life events modulate the neural basis of fear acquisition and extinction. PLoS One 7, e44352. Epub Sep 5. PMID: 22957066.

  • Herrick-Davis, K. (2013). Functional significance of serotonin receptor dimerization. Exp. Brain Res. 230, 375–386.

  • Hill, R.A., Murray, S.S., Halley, P.G., Binder, M.D., Martin, S.J., and van den Buuse, M. (2011). Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT(2C) receptor knockout mice. Hippocampus 21, 434–445. [Crossref]

  • Hindi Attar, C., Finckh, B. and Büchel, C. (2012). The influence of serotonin on fear learning. PLoS One 7, e42397.

  • Hirano, K., Piers, T.M., Searle, K.L., Miller, N.D., Rutter, A.R., and Chapman, P.F. (2009). Procognitive 5-HT6 antagonists in the rat forced swimming test: potential therapeutic utility in mood disorders associated with Alzheimer’s disease. Life Sci. 84, 558–562. [Crossref]

  • Hirst, W.D., Abrahamsen, B., Blaney, F.E., Calver, A.R., Aloj, L., Price, G.W., and Medhurst, A.D. (2003). Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol. Pharmacol. 64, 1295–1308. [Crossref]

  • Hirst, W.D., Stean, T.O., Rogers, D.C., Sunter, D., Pugh, P., Moss, S.F., Bromidge, S.M., Riley, G., Smith, D.R., Bartlett, S., et al. (2006). SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur. J. Pharmacol. 553, 109–119.

  • Hodges, H., Sowinski, P., Turner, J.J., and Fletcher, A. (1996). Comparison of the effects of the 5-HT3 receptor antagonists WAY-100579 and ondansetron on spatial learning in the water maze in rats with excitotoxic lesions of the forebrain cholinergic projection system. Psychopharmacology (Berl.) 125, 146–161.

  • Hoeffer, C.A. and Klann, E. (2010). mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci. 33, 67–75. [PubMed] [Crossref]

  • Holenz, J., Pauwels, P.J., Díaz, J.L., Mercè, R., Codony, X., and Buschmann, H. (2006). Medicinal chemistry strategies to 5-HT6 receptor ligands as potential cognitive enhancers and antiobesity agents. Drug Discov. Today. 11, 283–299. [Crossref]

  • Hong, E. and Meneses, A. (1996). Systemic injection of p-chloroamphetamine eliminates the effect of the 5-HT3 compounds on learning. Pharmacol. Biochem. Behav. 53, 765–769. [Crossref]

  • Hong, E., Orozco, G., Meneses, A., and Fillion, G. (1999). Effect of 5-HT-moduline, an endogenous peptide, in associative learning. Proc. West Pharmacol. Soc. 42, 37–38.

  • Hölscher, C. (1997). Long-term potentiation: a good model for learning and memory? Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 47–68. [PubMed] [Crossref]

  • Horiguchi, M., Huang, M., and Meltzer, H.Y. (2011). The role of 5-hydroxytryptamine 7 receptors in the phencyclidine-induced novel object recognition deficit in rats. J. Pharmacol. Exp. Ther. 338, 605–614.

  • Horiguchi, M., Hannaway, K.E., Adelekun, A.E., Huang, M., Jayathilake, K., and Meltzer, H.Y. (2013). D(1) receptor agonists reverse the subchronic phencyclidine (PCP)-induced novel object recognition (NOR) deficit in female rats. Behav. Brain Res. 238, 36–43.

  • Horisawa, T., Nishikawa, H., Toma, S., Ikeda, A., Horiguchi, M., Ono, M., Ishiyama, T., and Taiji, M. (2013). The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone. Behav. Brain Res. 244, 66–69. [Crossref]

  • Hotte, M., Dauphin, F., Freret, T., Boulouard, M., and Levallet, G. (2012). A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat. PLoS One 7,e32244.

  • Hoyer, D., Clarke, D.E., Fozard, J.R., Hartig, P.R., Martin, G.R., Mylecharane, E.J., Saxena, P.R., and Humphrey, P.P. (1994). International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 46, 157–203.

  • Hoyer, D., Hannon, J.P., and Martin, G.R. (2002). Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol. Biochem. Behav. 7, 533–554. [Crossref]

  • Huang, M., Panos, J.J., Kwon, S., Oyamada, Y., Rajagopal, L., and Meltzer, H.Y. (2014). Comparative effect of lurasidone and blonanserin on cortical glutamate, dopamine, and acetylcholine efflux: role of relative serotonin (5-HT)2A and DA D2 antagonism and 5-HT1A partial agonism. J. Neurochem. 128, 938–949. [Crossref]

  • Huerta-Rivas, A., González-Espinosa, C., Pérez-García., G., and Meneses, A. (2007). 5-HT6 receptor mRNA role during memory formation. Society for Neuroscience Meeting. Abstract No. 743.3/AAA26. San Diego, CA. November 3–7.

  • Huerta-Rivas, A., Perez-Garcia, G., Gonzalez, C., and Meneses, A. (2010). Time-course of 5-HT6 receptor mRNA expression during memory consolidation and amnesia. Neurobiol. Learn Mem. 93, 99–110. [Crossref]

  • Iadecola, C. (2004). Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat. Rev. Neurosci. 5,347–360. [PubMed] [Crossref]

  • Ishibashi, T., Horisawa, T., Tokuda, K., Ishiyama, T., Ogasa, M., Tagashira, R., Matsumoto, K., Nishikawa, H., Ueda, Y., Toma, S., et al. (2010). Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J. Pharmacol. Exp. Ther. 334, 171–181.

  • Ivachtchenko, A.V. and Ivanenkov, Y.A. (2012). 5HT6 receptor antagonists: a patent update. Part 1. Sulfonyl derivatives. Expert Opin. Ther. Pat. 22, 917–964. [Crossref]

  • Ivachtchenko, A.V., Ivanenkov, Y.A., and Skorenko, A.V. (2012). 5-HT6 receptor modulators: a patent update. Part 2. Diversity in heterocyclic scaffolds. Expert Opin. Ther. Pat. 22, 1123–1168. [Crossref]

  • Izquierdo, I. (1989). Mechanism of action of scopolamine as an amnesic. Trends Pharmacol. Sci. 10, 175–177. [Crossref]

  • Izquierdo, I., Medina, J.H., Viana, M.R.M., Izquierdo, L.A., and Izquierdo, I. (1999). Separate mechanisms of short- and long-term memory. Behav. Brain Res. 103, 1–11. [Crossref]

  • Izquierdo, I. and McGaugh, J.L. (2000). Behavioural pharmacology and its contribution to the molecular basis of memory consolidation. Behav. Pharmacol. 11, 517–534. [Crossref] [PubMed]

  • Izquierdo, I., Bevilaqua, L.R., Rossato, J.I., Bonini, J.S., Da Silva, W.C., Medina, J.H., and Cammarota, M. (2006a). The connection between the hippocampal and the striatal memory systems of the brain: a review of recent findings. Neurotox. Res. 10, 113–121. [Crossref]

  • Izquierdo, I., Bevilaqua, L.R., Rossato, J.I., Bonini, J.S., Medina, J.H., and Cammarota M. (2006b). Different molecular cascades in different sites of the brain control memory consolidation. Trends Neurosci. 29, 496–505. [Crossref] [PubMed]

  • Jacobs, B.L. and Azmitia, E.C. (1992). Structure and function of the brain serotonin system. Physiol. Rev. 72, 165–229. [PubMed]

  • Johnson, C.N., Ahmed, M., and Miller, N.D. (2008). 5-HT6 receptor antagonists: prospects for the treatment of cognitive disorders including dementia. Curr. Opin. Drug Discov. Devel. 11, 642–654.

  • Jones, T. and Moller, M.D. (2011). Implications of hypothalamic-pituitary-adrenal axis functioning in posttraumatic stress disorder. J. Am. Psychiatr. Nurses. Assoc. 17, 393–403.

  • Kandel, E.R. (2001). The molecular biology of memory storage: a dialogue between genes and synapses. Sci. 294, 1030–1038. [Crossref]

  • Kandel, E.R. (2012). The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain. 5, 14.

  • Kakade, S. and Dayan, P. (2002). Acquisition and extinction in autoshaping. Psychol. Rev. 109, 533–544. [Crossref] [PubMed]

  • Kalueff, A.V., Olivier, J.D., Nonkes, L.J., and Homberg, J.R. (2010). Conserved role for the serotonin transporter gene in rat and mouse neurobehavioral endophenotypes. Neurosci. Biobehav. Rev. 34, 373–386. [Crossref] [PubMed]

  • Karabeg, M.M., Grauthoff, S., Kollert, S.Y., Weidner, M., Heiming, R.S., Jansen, F., Popp, S., Kaiser, S., Lesch, K.P., Sachser, N., et al. (2013). 5-HTT Deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the morris water maze but not in the barnes maze. Plos One 8, 1–19.

  • Kendall, I., Slotten, H.A., Codony, X., Burgueño, J., Pauwels, P.J., Vela, J.M., and Fone, K.C. (2011). E-6801, a 5-HT6 receptor agonist, improves recognition memory by combined modulation of cholinergic and glutamatergic neurotransmission in the rat. Psychopharmacology (Berl.) 213, 413–430.

  • Kikuchi, C., Suzuki, H., Hiranuma, T., and Koyama, M. (2003). New tetrahydrobenzindoles as potent and selective 5-HT7 antagonists with increased in vitro metabolic stability. Bioorg. Med. Chem. Lett. 13, 61–64. [Crossref]

  • King, M.V., Sleight, A.J., Woolley, M.L., Topsham, I.A., Marsden, D.A., and Fone K.C. (2004). 5-HT6 receptors antagonists reverse delay-dependent deficits in novel object discrimination by enhancing consolidation – an effect sensitive to NMDA receptor antagonism. Neuropharmacology 47, 195–204. [Crossref]

  • King, M.V., Marsden, C.A., and Fone, K.C. (2008). A role for the 5-HT1A, 5-HT4 and 5-HT6 receptors in learning and memory. Trends Pharmacol. Sci. 29, 482–492. [Crossref]

  • King, M.V., Spicer, C.H., Sleight, A.J., Marsden, C.A., and Fone, K.C. (2009). Impact of regional 5-HT depletion on the cognitive enhancing effects of a typical 5-ht6 receptor antagonist, Ro 04-6790, in the Novel Object Discrimination task. Psychopharmacol (Berl.) 202, 111–123.

  • King, M., Negm, O., Tighe, P., Knapp, S., Wigmore, P., and Fone, K.C. (2012). Effect of the 5-HT6 receptor antagonist, SB-399885, on cognition, hippocampal cell proliferation and protein expression in the neurodevelopmental model of schizophrenia. Serotonin Club meeting, Abstract p. 60. July 10–12, 2012. Montpellier, France.

  • Koenig, P., Smith, E.E., Troiani, V., Anderson, C., Moore, P., and Grossman, M. (2009). Medial temporal lobe involvement in an implicit memory task: evidence of collaborating implicit and explicit memory systems from FMRI and Alzheimer’s disease. Cereb Cortex 18, 2831–2843.

  • Krishnamurthy, S., Garabadu, D., and Joy, K.P. (2013). Risperidone ameliorates post-traumatic stress disorder-like symptoms in modified stress re-stress model. Neuropharmacology 75, 62–77. [Crossref] [PubMed]

  • Lacivita, E., Di Pilato, P., De Giorgio, P., Colabufo, N.A., Berardi, F., Perrone, R., and Leopoldo, M. (2012). The therapeutic potential of 5-HT1A receptors: a patent review. Expert Opin. Ther. Pat. 22, 887–902. [Crossref]

  • Lamprecht, R. (2014). Actin cytoskeleton in memory formation. Prog. Neurobiol. Feb 12. pii: S0301-0082(14)00016-1. doi: 10.1016/j.pneurobio.2014.02.001. [Epub ahead of print] PMID: 24530292. [Crossref]

  • Landry, C.D., Kandel, E.R., and Rajasethupathy, P. (2013). New mechanisms in memory storage: piRNAs and epigenetics. Trends Neurosci. 36, 535–542. [PubMed] [Crossref]

  • Leopoldo, M., Lacivita, E., De Giorgio, P., Fracasso, C., Guzzetti, S., Caccia, S., Contino, M., Colabufo, N.A., Berardi, F., and Perrone, R. (2008). Structural modifications of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamides: influence on lipophilicity and 5-HT7 receptor activity. Part III. J. Med. Chem. 51, 5813–5822.

  • Leopoldo, M., Lacivita, E., Berardi, F., and Perrone, R. (2010). 5-HT7 receptor modulators: a medicinal chemistry survey of recent patent literature (2004–2009). Expert Opin. Ther. Pat. 20, 739–754. [Crossref]

  • Lesch, K.P. and Waider, J. (2012). Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. Neuron 76, 175–191. doi: 10.1016/j.neuron.2012.09.013. PMID: 23040814 [PubMed – in process] [Crossref] [PubMed]

  • Li, Z., Huang, M., Prus, A.J., Dai, J., and Meltzer, H.Y. (2007). 5-HT6 receptor antagonist SB-399885 potentiates haloperidol and risperidone-induced dopamine efflux in the medial prefrontal cortex or hippocampus Brain Res. 1134, 70–78.

  • Lieben, C.K.J., Blokland, A., Sik, A., Sung, E., van Nieuwenhuizen, P., and Schreiber, R. (2005). The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat. Neuropsychopharmacology 30, 2169–2179. [Crossref]

  • Liem-Moolenaar, M., Rad, M., Zamuner, S., Cohen, A.F., Lemme, F., Franson, K.L., van Gerven J.M., and Pich E.M. (2011). Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men. Br. J. Clin. Pharmacol. 71, 907–916. [Crossref]

  • Linden, R., Martins, V.R., Prado, M.A., Cammarota, M., Izquierdo, I., and Brentani, R.R. (2008). Physiology of the prion protein. Physiol. Rev. 88, 673–728. [PubMed] [Crossref]

  • Lindner, M.D., Hodges, D.B. Jr., Hogan, J.B., Orie, A.F., Corsa, J.A., Barten, D.M., Polson, C., Robertson, B.J., Guss, V.L., Gillman, K.W., et al. (2003). An assessment of the effects of serotonin 6 (5-HT6) receptor antagonists in rodent models of learning. J. Pharmacol. Exp. Ther. 307, 682–691.

  • Liu, G.L. and Robichaud, A.J. (2009). 5-HT6 antagonists as potential treatment for cognitive dysfunction. Drug Develop. Res. 70, 145–168. [Crossref]

  • Liu, R.Y., Shah, S., Cleary, L.J., and Byrne, J.H. (2011). Serotonin- and training-induced dynamic regulation of CREB2 in Aplysia. Learn Mem. 18, 245–249.

  • Liy-Salmeron, G. and Meneses, A. (2007). Role of 5-HT1-7 receptors in short- and long-term memory for an autoshaping task: intrahippocampal manipulations. Brain Res. 1147, 140–147.

  • Lladó-Pelfort, L., Santana, N., Ghisi, V., Artigas, F., and Celada, P. (2012). 5-HT1A receptor agonists enhance pyramidal cell firing in prefrontal cortex through a preferential action on GABA interneurons. Cereb. Cortex 22, 1487–1497. [Crossref]

  • Loiseau, F., Dekeyne, A., and Millan, M.J. (2008). Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex. Psychopharmacology (Berl.) 196, 93–104.

  • Lorke, D.E., Lu, G., Cho, E., and Yew, D.T. (2005). Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients. BMC Neurosci. 6, 36.

  • Ly, S., Pishdari, B., Lok, L.L., Hajos, M., and Kocsis, B. (2013). Activation of 5HT6 receptors modulates sleep-wake activity and hippocampal Theta oscillation. ACS Chem. 4, 191–199.

  • Lynch, M.A. (2004). Long term potentiation. Physiol. Rev. 84, 87–136. [Crossref] [PubMed]

  • Lynch, G., Kramár, E.A., Babayan, A.H., Rumbaugh, G., and Gall, C.M. (2013). Differences between synaptic plasticity thresholds result in new timing rules for maximizing long-term potentiation. Neuropharmacology 64, 27–36. [PubMed] [Crossref]

  • Mahar, I., Bambico, F.R., Mechawar, N., and Nobrega, J.N. (2014). Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci. Biobehav. Rev. 38, 173–192. [Crossref] [PubMed]

  • Maher-Edwards, G., Zvartau-Hind, M., Hunter, A.J., Gold, M., Hopton, G., Jacobs, G., Davy, M., and Williams, P. (2009). Double-blind, controlled Phase II study of a 5-HT6 receptor antagonist, SB-742457. Curr. Alzheimer Res. 7, 374–385.

  • Manuel-Apolinar, L. and Meneses, A. (2004). 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production. Behav. Brain Res. 148, 179–184. [Crossref]

  • Manuel-Apolinar, L., Rocha, L., Pascoe, D., Castillo, E., Castillo, C., and Meneses, A. (2005). Modifications of 5-HT4 receptor expression in rat brain during memory consolidation. Brain Res. 1042, 73–81.

  • Mar, A.C., Horner, A.E., Nilsson, S.R., Alsiö, J., Kent, B.A., Kim, C.H., Holmes, A., Saksida, L.M. and Bussey, T.J. (2013). The touchscreen operant platform for assessing executive function in rats and mice. Nat. Protoc. 8, 1985–2005. [Crossref] [PubMed]

  • Marazziti, D., Baroni, S., Pirone, A., Giannaccini, G., Betti Schmid, L., Vatteroni, E., Palego, L., Borsini, F., Bordi, F., Piano, I., et al. (2012). Distribution of serotonin receptor of type 6 (5-HT6) in human brain post-mortem. A pharmacology, autoradiography and immunohistochemistry study. Neurochem. Res. 37, 920–927.

  • Marcos, B., Gil-Bea, F.J., Hirst, W.D., García-Alloza, M., and Ramírez, M.J. (2006). Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release. Eur. J. Neurosci. 24, 299–1306.

  • Marcos, B., García-Alloza, M., Gil-Bea, F.J., Chuang, T.T., Francis, P.T., Chen, C.P., Tsang, S.W., Lai, M.K., and Ramirez, M.J. (2008). Involvement of an altered 5-HT6 receptor function in behavioral symptoms of Alzheimer’s disease. J. Alzheimer’s Dis. 14, 43–50.

  • Marcos, B., Cabero, M., Solas, M., Aisa, B., and Ramirez, M.J. (2010). Signaling pathways associated with 5-HT6 receptors: relevance for cognitive effects. Int. J. Neuropsychopharmacol. 9, 1–10.

  • Marin, P., Meffre, J., Chaumont-Dubel, S., La Cour, C.L., Loiseau, F., Watson, D.J.G., Dekeyne, A., Martial Séveno, M., Déléris, P., Fone, K.C.F., et al. (2012a). 5-HT6 receptors disrupt cognition by recruiting mTOR: relevance to schizophrenia. Serotonin Club Meeting, Abstract p: 58. July 10–12. Montpellier, France.

  • Marin, P., Becamel, C., Dumuis, A., and Bockaert, J. (2012b). 5-HT receptor-associated protein networks: new targets for drug discovery in psychiatric disorders? Curr. Drug Targets 13, 28–52. [Crossref]

  • Marshall, J.F. and O’Dell, S.J. (2012). Methamphetamine influences on brain and behavior: unsafe at any speed? Trends Neurosci. 35, 536–545. [Crossref]

  • Martin, C. and Sibson, N.R. (2008).Pharmacological MRI in animal models: a useful tool for 5-HT research? Neuropharmacology 55, 1038–1047. [Crossref]

  • Martyn, A.C., De Jaeger, X., Magalhães, A.C., Kesarwani, R., Gonçalves, D.F., Raulic, S., Guzman, M.S., Jackson, M.F., Izquierdo I., Macdonald, J.F., et al. (2012). Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation. Proc. Natl. Acad. Sci. USA 109, 17651–17656. [Crossref]

  • Mathur, B.N. and Lovinger, D.M. (2012). Serotonergic action on dorsal striatal function. Parkinsonism Relat. Disord. 18, S129–S131.

  • Matthys, A., Haegeman, G., Van Craenenbroeck, K., and Vanhoenacker, P. (2011). Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives. Mol. Neurobiol. 43, 228–253. [Crossref]

  • McGaugh, J.L. (1966). Time-dependent processes in memory storage. Science 153, 1351–1358. [PubMed] [Crossref]

  • McGaugh, J.L. (1989). Dissociating learning and performance: drug and hormone enhancement of memory storage. Brain Res. Bull. 4–5, 339–345. [Crossref]

  • McGaugh, J.L. (2006). Make mild moments memorable: add a little arousal. Trends Cogn. Sci. 10, 345–347. [Crossref] [PubMed]

  • McGaugh, J.L. (2013). Making lasting memories: remembering the significant. Proc. Natl. Acad. Sci. USA 110 Suppl 2, 10402–10407. [Crossref]

  • McIntosh, A.L., Ballard, T.M., Steward, L.J., Moran, P.M., and Fone, K.C. (2013). The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats. Psychopharmacology (Berl). 228, 31–42.

  • Means, A.R. (2008). The year in basic science: calmodulin kinase cascades. Mol. Endocrinol. 22, 2759–2765. [Crossref] [PubMed]

  • Meffre, J., Chaumont-Dubel, S., Mannoury la Cour, C., Loiseau, F., Watson, D.J., Dekeyne, A., Séveno, M., Rivet, J.M., Gaven, F., and Déléris, P. (2012). 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia. EMBO Mol. Med. 4, 1043–1056. [Crossref]

  • Meltzer, H.Y. (2012). Clozapine: balancing safety with superior antipsychotic efficacy. Clin. Schizophr. Relat. Psychoses 6, 134–144. [Crossref] [PubMed]

  • Meltzer, H.Y., Rajagopal, L., Huang, M., Oyamada, Y., Kwon, S., and Horiguchi, M. (2013). Translating the N-methyl-D-aspartate receptor antagonist model of schizophrenia to treatments for cognitive impairment in schizophrenia. Int. J. Neuropsychopharmacol. 16, 2181–2194. [Crossref]

  • Meneses, A. (1999). 5-HT system and cognition. Neurosci. Biobehav. Rev. 23, 1111–1125. [Crossref]

  • Meneses, A. (2001a). Role of 5-HT6 receptors in memory formation. Drug News Perspect. 14, 396–400. [Crossref]

  • Meneses, A. (2001b). Effects of the 5-HT6 receptor antagonist Ro 04-6790 on learning consolidation. Behav. Brain Res. 118, 107–110. [Crossref]

  • Meneses, A. (2001c). Could the 5-HT1B receptor inverse agonism affect learning consolidation? Neurosci. Biobehav. Rev. 25, 193–201. [Crossref]

  • Meneses, A. (2002). Tianeptine: 5-HT uptake sites and 5-HT1-7 receptors modulate memory formation in an autoshaping Pavlovian/instrumental task. Neurosci. Biobehav. Rev. 26, 309–319. [Crossref]

  • Meneses, A. (2003). Pharmacological analysis of an associative learning task: 5-HT1 to 5-HT7 receptor subtypes function on a Pavlovian/instrumental autoshaped memory. Learn. Mem. 10, 363–372. [Crossref]

  • Meneses, A. (2004). Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task. Behav. Brain Res. 155, 275–282. [Crossref]

  • Meneses, A. (2007a). Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2A, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory. Behav. Brain Res. 184, 81–90.

  • Meneses, A. (2007b). Do serotonin1-7 receptors modulate short and long-term memory? Neurobiol. Learn Mem. 87, 561–572. [Crossref]

  • Meneses, A. (2013). 5-HT systems: emergent targets for memory formation and memory alterations. Rev. Neurosci. 24, 629–664.

  • Meneses, A. (2014). Neurotransmitters and Memory: Cholinergic, Glutamatergic, GaBAergic, Mdopaminergic, Serotonergic, Signaling, and Memory. Identification of Neural Markers Accompanying Memory. A. Meneses, ed. (San Diego, USA: Elsevier), pp. 5–45.

  • Meneses, A. and Hong, E. (1997). A pharmacological analysis of serotonergic receptors: effects of their activation of blockade in learning. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 273–296. [PubMed] [Crossref]

  • Meneses, A. and Liy-Salmeron, G. (2012). Serotonin and emotion, learning and memory. Rev. Neurosci. 23, 443–453.

  • Meneses, A. and Perez-Garcia, G. (2007). 5-HT1A receptors and memory. Neurosci. Biobehav. Rev. 3, 705–27. [Crossref]

  • Meneses, A., Manuel-Apolinar, L., Castillo, C., and Castillo, E. (2007). Memory consolidation and amnesia modify 5-HT6 receptors expression in rat brain: an autoradiographic study. Behav. Brain Res. 178, 53–61. [Crossref]

  • Meneses, A., Perez-Garcia, G., Liy-Salmeron, G., Flores-Galvez, D., Castillo, C., and Castillo, E. (2008). The effects of the 5-HT6 receptor agonist EMD and the 5-HT7 receptor agonist AS19 on memory formation. Behav. Brain Res. 195, 112–119.

  • Meneses, A., Perez-Garcia, G., Liy-Salmeron, G., Ponce-Lopez, T., Tellez, R., and Flores-Galvez, D. (2009). Associative Learning, Memory and Serotonin: A Neurobiological and Pharmacological Analysis. Models of Neuropharmacology. L.L. Rocha Arrieta, and V. Granados-Soto, eds. (Transworld Research Network. Trivandrum-695 023, Kerala, India). pp. 169–182.

  • Meneses, A., Pérez-García, G., Ponce-Lopez, T., and Castillo, C. (2011a). 5-HT6 receptor memory and amnesia: behavioral pharmacology – learning and memory processes. Int. Rev. Neurobiol. 96, 27–47. [Crossref]

  • Meneses, A., Perez-Garcia, G., Ponce-Lopez, T., Tellez, R., and Castillo, C. (2011b). Serotonin transporter and memory. Neuropharmacology 61, 355–363. [PubMed] [Crossref]

  • Mestre, T.A., Zurowski, M., and Fox, S.H. (2013). 5-Hydroxytryptamine 2A receptor antagonists as potential treatment for psychiatric disorders. Expert Opin. Investig. Drugs 22, 411–421. [Crossref]

  • Meyer, J.H. (2012). Neuroimaging markers of cellular function in major depressive disorder: implications for therapeutics, personalized medicine, and prevention. Clin. Pharmacol. Ther. 91, 201–214. [Crossref] [PubMed]

  • Millan, M.J., Gobert, A., Roux, S., Porsolt, R., Meneses, A., Carli, M., Di Cara, B., Jaffard, R., Rivet, J.M., Lestage, P., et al. (2004). The serotonin1A receptor partial agonist S15535 [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine] enhances cholinergic transmission and cognitive function in rodents: a combined neurochemical and behavioral analysis. J. Pharmacol. Exp. Ther. 311, 190–203.

  • Millan, M.J., Marin, P., Bockaert, J., and la Cour, C.M. (2008). Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions. Trends Pharmacol. Sci. 29, 454–464. [Crossref]

  • Millan, M.J., Agid, Y., Brüne, M., Bullmore, E.T., Carter, C.S., Clayton, N.S., Connor, R., Davis, S., Deakin, B., DeRubeis, R.J., et al. (2012). Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 11, 141–168. [Crossref] [PubMed]

  • Mitchell, E.S. and Neumaier, J.F. (2005). 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacol. Ther. 108, 320–333. [Crossref]

  • Mitchell, E.S., Sexton, T., and Neumaier, J.F. (2007). Increased expression of 5-HT6 receptors in the rat dorsomedial striatum impairs instrumental learning. Neuropsychopharmacology 32, 1520–1530. [Crossref]

  • Mitchell, E.S., McDevitt, R.A., and Neumaier, J.F. (2009). Adaptations in 5-HT receptor expression and function: implications for treatment of cognitive impairment in aging. J. Neurosci. Res. 87, 2803–2811. [Crossref]

  • Modica, M.N., Pittalà, V., Romeo, G., Salerno, L., and Siracusa, M.A. (2010). Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years. Curr. Med. Chem. 17, 334–362. [Crossref]

  • Molodtsova, G.F. (2008). Serotonergic mechanisms of memory trace retrieval. Behav. Brain Res. 195, 7–16.

  • Moret, C., Grimaldi, B., Massot, O., and Fillion, G. (2003). The role and therapeutic potential of 5-HT-moduline in psychiatry. Semin. Clin. Neuropsychiatry 8, 137–146. [Crossref]

  • Moyano, S., Del Río, J., and Frechilla, D. (2004). Role of hippocampal CaMKII in serotonin 5-HT1A receptor-mediated learning deficit in rats. Neuropsychopharmacology 29, 2216–2224. [Crossref]

  • Myhrer, T. (2003). Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res. Rev. 41, 268–287. [Crossref]

  • Na, C.H., Jones, D.R., Yang, Y., Wang, X., Xu, Y., and Peng, J. (2012). Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis. J. Proteome. Res. 11, 4722–4732. [Crossref]

  • Nikiforuk, A. and Popik, P. (2013). Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors. Behav. Brain Res. 248, 136–140.

  • Nikiforuk, A., Kos, T., Fijał, K., Hołuj, M., Rafa, D., and Popik, P. (2013). Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats. PLoS One 8, e66695.

  • Nordquist, N. and Oreland, L. (2010). Serotonin, genetic variability, behaviour, and psychiatric disorders – a review. Ups. J. Med. Sci. 115, 2–10.

  • Noristani, H.N., Verkhratsky, A., and Rodríguez, J.J. (2012). High tryptophan diet reduces CA1 intraneuronal β-amyloid in the triple transgenic mouse model of Alzheimer’s disease. Aging Cell 11, 810–822. [Crossref]

  • Ögren, S.O., Eriksson, T.M., Elvander-Tottie, E., D’Addario, C., Ekström, J.C., Svenningsson, P., Meister, B., Kehr, J., and Stiedl, O. (2008). The role of 5-HT1A receptors in learning and memory. Behav. Brain Res. 195, 54–77.

  • Owen, G.R. and Brenner, E.A. (2012). Mapping molecular memory: navigating the cellular pathways of learning. Cell. Mol. Neurobio. 32, 919–941. [Crossref]

  • Packard, M.G. and Knowlton, B.J. (2002). Learning and memory functions of the basal ganglia. Ann. Rev. Neurosci. 25, 563–593. [Crossref]

  • Pappatà, S., Salvatore, E., and Postiglione, A. (2008). In vivo imaging of neurotransmission and brain receptors in dementia. J. Neuroimaging 18, 111–124. [Crossref]

  • Park, S.M. and Williams, C.L. (2012). Contribution of serotonin type 3 receptors in the successful extinction of cued or contextual fear conditioned responses: interactions with GABAergic signaling. Rev. Neurosci. 23, 555–569.

  • Pattij, T. (2002). 5-HT1A receptor knockout mice and anxiety: behavioral and physiological studies. (Ph.D. thesis, Universiteit Utrecht, The Netherlands.)

  • Peele, D.B. and Vincent, A. (1989). Strategies for assessing learning and memory, 1978–1987: a comparison of behavioral toxicology, psychopharmacology, and neurobiology. Neurosci. Biobehav. Rev. 13, 317–322.

  • Perez-García, G. and Meneses, A. (2005). Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task. Pharmacol. Biochem. Behav. 81, 673–682.

  • Perez-Garcia, G. and Meneses, A. (2009). Memory time-course: mRNA 5-HT1A and 5-HT7 receptors. Behav. Brain Res. 202, 102–113. [Crossref]

  • Pérez-García, G. and Meneses, A. (2008a). Memory formation, amnesia, improved memory and reversed amnesia: 5-HT role. Behav. Brain Res. 195, 17–29.

  • Pérez-García, G. and Meneses, A. (2008b). Ex-vivo study of 5-HT1A and 5-HT7 receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia. Behav. Brain Res. 195, 139–146.

  • Pérez-García, G., González-Espinosa, C., and Meneses, A. (2006). An mRNA expression analysis of stimulation and blockade of 5-HT7 receptors during memory consolidation. Behav. Brain Res. 169, 83–92. [Crossref]

  • Pérez-Torres, S., Cortés, R., Tolnay, M., Probst, A., Palacios, J.M., and Mengod, G. (2003). Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer’s disease brains examined by in situ hybridization. Exp. Neurol. 182, 322–334.

  • Pignataro, G., Capone, D., Polichetti, G., Vinciguerra, A., Gentile, A., Di Renzo, G., and Annunziato, L. (2011). Neuroprotective, immunosuppressant and antineoplastic properties of mTOR inhibitors: current and emerging therapeutic options. Curr. Opin. Pharmacol. 11, 378–394. [Crossref]

  • Pittala, V. and Pittala, D. (2011). Latest advances towards the discovery of 5-HT7 receptor ligands. Mini. Rev. Med. Chem. 11, 1108d//21. [Crossref]

  • Puig, M.V. and Gulledge, A.T. (2011). Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol. Neurobiol. 44, 449–464. [Crossref] [PubMed]

  • Radley, J.J., Farb, C.R., He, Y., Janssen, W.G., Rodrigues, S.M., Johnson, L.R., Hof, P.R., LeDoux, J.E., and Morrison, J.H. (2007). Distribution of NMDA and AMPA receptor subunits at thalamo-amygdaloid dendritic spines. Brain. Res. 1134, 87–94.

  • Rajasethupathy, P., Antonov, I., Sheridan, R., Frey, S., Sander, C., Tuschl, T., and Kandel, E.R. (2012). A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149, 693–707. [PubMed] [Crossref]

  • Ramírez, M.J. (2013). 5-HT6 receptors and Alzheimer’s disease. Alzheimers Res. Ther. 5, 15.

  • Rapanelli, M., Frick, L.R., Bernardez-Vidal, M., and Zanutto, B.S. (2013). Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits. Behav. Brain Res. 257C, 156–165.

  • Raymond, J.R., Mukhin, Y.V., Gelasco, A., Turner, J., Collinsworth, G., Gettys, T.W., Grewal, J.S., and Garnovskaya, M.N. (2001). Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol. Ther. 92, 179–212. [PubMed] [Crossref]

  • Raymond, J.R., Turner, J.H., Gelasco, A.K., Ayiku, H.B., Coaxum, S.D., Arthur, J.M., and Garnovskaya, M.N. (2006). The Serotonin Receptors. N.J. Totowa and B.L. Roth, ed., (Human Press, N.J. Totowa), pp. 143–2006.

  • Reis, H.J., Guatimosim, C., Paquet, M., Santos, M., Ribeiro, F.M., Kummer, A., Schenatto, G., Salgado, J.V., Vieira, L.B., Teixeira, A.L. et al. (2009). Neuro-transmitters in the central nervous system and their implication in learning and memory processes. Curr. Med. Chem. 16, 796–840. [Crossref] [PubMed]

  • Reid, M., Carlyle, I., Caulfield, W.L., Clarkson, T.R., Cusick, F., Epemolu, O., Gilfillan, R., Goodwin, R., Jaap, D., O’Donnell, E.C., et al. (2010). The discovery and SAR of indoline-3-carboxamides – A new series of 5-HT6 antagonists. Bioorg. Med. Chem. Lett. 20, 3713–3716. [Crossref]

  • Renner, U., Zeug, A., Woehler, A., Niebert, M., Dityatev, A., Dityateva, G., Gorinski, N., Guseva, D., Abdel-Galil, D., Fröhlich, M., et al. (2012). Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking. J. Cell. Sci. 125, 2486–2499. [Crossref]

  • Richter, J.D. and Klann, E. (2009). Making synaptic plasticity and memory last: mechanisms of translational regulation. Genes Dev. 23, 1–11. [Crossref] [PubMed]

  • Riekkinen, M., Sirviö, J., Toivanen, T., and Riekkinen, P. Jr. (1995). Combined treatment with a 5HT1A receptor agonist and a muscarinic acetylcholine receptor antagonist disrupts water maze navigation behavior. Psychopharmacology (Berl) 122, 137–146. [Crossref]

  • Riemer, C., Borroni, E., Levet-Trafit, B., Martin, J.R., Poli, S., Porter, R.H.P., and Bös, M. (2003). Influence of the 5-HT6 receptor on acetylcholine release in the cortex: pharmacological characterization of 4-(2-Bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a potent and selective 5-HT6 receptor antagonist. J. Med. Chem. 46, 1273–1276. [Crossref]

  • Roberts, A.J. and Hedlund, P.B. (2012). The 5-HT7 receptor in learning and memory. Hippocampus 22, 762–771. [Crossref]

  • Roberts, J.C., Reavill, C., East, S.Z., Harrison, P.J., Patel, S., Routledge, C., and Leslie, R.A. (2002). The distribution of 5-HT6 receptors in rat brain: an autoradiographic binding study using the radiolabeled 5-HT6 receptor antagonist [125I]SB-258585. Brain Res. 934, 49–57.

  • Roberts, P.D., Spiros, A., and Geerts, H. (2012). Simulations of symptomatic treatments for Alzheimer’s disease: computational analysis of pathology and mechanisms of drug action. Alzheimers Res Ther. 4, 50. [Epub ahead of print] PMID: 23181523. [Crossref]

  • Rodríguez, J.J., Noristani, H.N., and Verkhratsky, A. (2012). The serotonergic system in ageing and Alzheimer’s disease. Prog Neurobiol. 99, 15–41. [PubMed] [Crossref]

  • Rogers, D.C., and Hagan, J.J. (2001). 5-HT6 receptor antagonists enhance retention of a water maze task in the rat. Psychopharmacology (Berl.) 158, 114–119.

  • Romero, G., Sánchez, E., Pujol, M., Pérez, P., Codony, X., Holenz, J., Buschmann, H., and Pauwels, P.J. (2006). Efficacy of selective 5-HT6 receptor ligands determined by monitoring 5-HT6 receptor-mediated cAMP signaling pathways. Br. J. Pharmacol. 148, 1133–1143.

  • Rossé, G. and Schaffhauser, H. (2010). 5-HT6 receptor antagonists as potential therapeutics for cognitive impairment. Curr. Top Med. Chem. 10, 207–221. [Crossref]

  • Roth, B.L., Hanizavareh, S.M., and Blum, A.E. (2004). Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacol (Berl.) 174, 17–24.

  • Ruat, M., Traiffort, E., Arrang, J.M., Tardivel-Lacombe, J., Diaz, J., Leurs, R., and Schwartz, J.C. (1993). A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation. Biochem. Biophys. Res. Com. 193, 268–276. [Crossref]

  • Ruotsalainen, S., Miettinen, R., MacDonald, E., Riekkinen, M., and Sirviö, J. (1998). The role of the dorsal raphe-serotonergic system and cholinergic receptors in the modulation of working memory. Neurosci. Biobehav. Rev. 22, 21–31. [PubMed]

  • Ruiz, N.V. and Oranias, G.O. (2010). Patents. Int Rev Neurobiol. 5-HT6 receptors, Part I. F Borsini, ed. (Oxford: Elsevier, Academic Press), pp. 36–66.

  • Russell, M.G. and Dias, R. (2002). Memories are made of this (perhaps): a review of serotonin 5-HT6 receptor ligands and their biological functions. Curr. Top Med. Chem. 2, 643–54. [Crossref]

  • Sakata, K. and Duke, S.M. (2014). Lack of BDNF expression through promoter IV disturbs expression of monoamine genes in the frontal cortex and hippocampus Neuroscience. 260, 265–275.

  • Santucci, A.C, and Cardiello, J. (2004). Memory reactivation in rats treated with the 5-HT1A agonist 8-OH-DPAT: a case of gone, but not forgotten. Behav. Neurosci. 118, 248–252. [Crossref]

  • Saulin, A., Savli, M., and Lanzenberger, R. (2012). Serotonin and molecular neuroimaging in humans using PET. Amino Acids 42, 2039–2057. [PubMed] [Crossref]

  • Schechter, L.E., Smith, D.L., Zhang, G.M., Li, P., Lin, Q., Rosenzweig-Lipson, S., Robichaud, A., Bernotas, R., and Beyer, C.E. (2004). WAY-466: pharmacological profile of a novel and selective 5-HT6 agonist. Inter. J. Neuropsychopharmacol. 7, S291.

  • Schechter, L.E., Smith, D.L., Rosenzweig-Lipson, S., Sukoff, S.J., Dawson, L.A., Marquis, K., Jones, D., Piesla, M., Andree, T., Nawoschik, S., et al. (2005). Lecozotan (SRA-333): a selective serotonin1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties. J. Exp. Pharmacol. Ther. 314, 1274–1289.

  • Schmitt, J.A., Wingen, M., Ramaekers, J.G., Evers, E.A., and Riedel, W.J. (2006). Serotonin and human cognitive performance. Curr. Pharm. Des. 12, 2473–2486. [Crossref] [PubMed]

  • Schreiber, R., Vivian, J., Hedley, L., Szczepanski, K., Secchi, R.L., Zuzow, M., van Laarhoven, S., Moreau, J.L., Martin, J.R., Sik, A., et al. (2007). Effects of the novel 5-HT6 receptor antagonist RO4368554 in rat models for cognition and sensorimotor gating. Eur. Neuropsychopharmacol. 17, 277–288. [Crossref]

  • Sghendo, L. and Mifsud, J. (2012). Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model. Pharm. Pharmacol. 64, 317–325. [Crossref]

  • Simon, N.W. and Setlow, B. (2006). Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: implications for drug addiction. Neurobiol. Learn Mem. 86, 305–310. [Crossref] [PubMed]

  • Skelton, M.R., Williams, M.T., and Vorhees, C.V. (2008). Developmental effects of 3,4-methylenedioxymethamphetamine: a review. Behav. Pharmacol. 19, 91–111. [Crossref]

  • Sleight, A., Boess, F.G., Bös, M., and Bourson, A. (1998). The putative 5-ht6 receptor: localization and function. Ann. NY Acad. Sci. 861, 91–96.

  • Smith, C., Rahman, T., Toohey, N., Mazurkiewicz, J., Herrick-Davis, K., and Teitler, M. (2006). Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor. Mol. Pharmacol. 70, 1264–1270. [Crossref]

  • Sossin, W.S. (2008). Defining memories by their distinct molecular traces. Trends Neurosci. 31, 170–175. [PubMed] [Crossref]

  • Speranza, L., Chambery, A., Di Domenico, M., Crispino, M., Severino, V., Volpicelli, F., Leopoldo, M., Bellenchi, G.C., di Porzio, U., and Perrone-Capano, C. (2013). The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling pathways. Neuropharmacology 67, 155–167.

  • Stahl, S.M. (2010). The serotonin-7 receptor as a novel therapeutic target. J. Clin. Psychiatry 71, 1414–1415.

  • Stahlman, W.D., Young, M.E., and Blaisdell, A.P. (2010). Response variability in pigeons in a Pavlovian task. Learn Behav. 38, 111–118. [Crossref]

  • Steckler, T. and Sahgal, A. (1995). The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour. Behav. Brain Res. 67, 165–199. [Crossref] [PubMed]

  • Stewart, A.J., Fox, A., Morimoto, B.H., and Gozes, I. (2007). Looking for novel ways to treat the hallmarks of Alzheimer’s disease. Expert Opin. Investig. Drugs 16, 1183–1196. [Crossref]

  • Sumiyoshi, T., Higuchi, Y., and Uehara, T. (2013). Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia. Front Behav. Neurosci. 16, 140.

  • Sweatt, J.D. (2009). Experience-dependent epigenetic modifications in the central nervous system. Biol. Psychiatry 65, 191–197. [Crossref] [PubMed]

  • Szczepanski, K.V., Vivian, J.A., Dorsch, K., Blokland, A., Hedley, I., Lieben, C.K.J., Martin, J.R., Secchi, R.L., Sik, A., Sung, E., et al. (2002). Precognitive effects of the 5-HT6 receptor antagonist in rats. Soc. Neurosci. Abstract 290, 29.

  • Tajiri, M., Hayata-Takano, A., Seiriki, K., Ogata, K., Hazama, K., Shintani, N., Baba, A., and Hashimoto, H. (2012). Serotonin 5-HT7 receptor blockade reverses behavioral abnormalities in PACAP-deficient mice and receptor activation promotes neurite extension in primary embryonic hippocampal neurons: therapeutic implications for psychiatric disorders. J. Mol. Neurosci. 48, 473–481. [Crossref]

  • Tarazi, F.I., and Riva, M.A. (2013). The preclinical profile of lurasidone: clinical relevance for the treatment of schizophrenia. Expert Opin. Drug Discov. 8, 1297–1307.

  • Talpos, J.C., Fletcher, A.C., Circelli, C., Tricklebank, M.D., and Dix, S.L. (2012). The pharmacological sensitivity of a touchscreen-based visual discrimination task in the rat using simple and perceptually challenging stimuli. Psychopharmacology (Berl.) 20, 221, 437–449.

  • Tellez, R., Gómez-Viquez, L., Liy-Salmeron, G., and Meneses, A. (2012a). GABA, glutamate, dopamine and serotonin transporters expression on forgetting. Neurobiol. Learn Mem. 98, 66–77. [PubMed] [Crossref]

  • Tellez, R., Gómez-Víquez, L., and Meneses, A. (2012b). GABA, glutamate, dopamine and serotonin transporters expression on memory formation and amnesia. Neurobiol. Learn Mem. 97, 189–201. [Crossref] [PubMed]

  • Tellez, R., Rocha, L., Castillo, C., and Meneses, A. (2010). Autoradiographic study of serotonin transporter during memory formation. Behav. Brain Res. 212, 12–26. [PubMed] [Crossref]

  • Terry, A.V., Jr., Buccafusco, J.J., and Wilson, C. (2008). Cognitive dysfunction in neuropsychiatric disorders: selected serotonin receptor subtypes as therapeutic targets. Behav. Brain Res. 195, 30–38.

  • Thompson, A.J. (2013). Recent developments in 5-HT3 receptor pharmacology. Trends Pharmacol. Sci. 34, 100–109. [Crossref]

  • Thuault, S. (2012). Cdk5 keeps memory on Trk. Nat. Neurosci. 15, 1474. [PubMed] [Crossref]

  • Timotijević, I., Stanković, Ž., Todorović, M., Marković, S.Z., and Kastratović, D.A. (2012). Serotonergic organization of the central nervous system. Psychiatr. Danub. 24, S326–S330.

  • Tomie, A., Lincks, M., Nadarajah, S.D., Pohorecky, L.A., and Yu, L. (2012). Pairings of lever and food induce Pavlovian conditioned approach of sign-tracking and goal-tracking in C57BL/6 mice. Behav. Brain Res. 226, 571–578. [Crossref]

  • Tremblay, M.A., Acker, C.M., and Davies, P. (2010). Tau phosphorylated at tyrosine 394 is found in Alzheimer’s disease tangles and can be a product of the Abl-related kinase. Arg. J. Alzheimers Dis. 19, 721–733.

  • Turner, J.N., Coaxum, SD., Gelasco, A.K., Garnovskaya, M.N., and Raymond, J.R. (2007). Calmodulin is a 5-HT Receptor-Interacting and Regulatory Protein. In: Serotonin Receptors in Neurobiology. A, Chattopadhyay ed., [Boca Raton (FL): CRC Press] Chapter. Available from: http://www.ncbi.nlm.nih.gov/books/NBK5202/

  • Upton, N., Chuang, T.T., Hunter, A.J., and Virley, D.J. (2008). 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease. Neurotherapeutics 5, 458–469. [Crossref]

  • van Praag, H.M. (2008). The cognitive paradox in posttraumatic stress disorder: a hypothesis. Prog. Neuropsychopharmacol. Biol. Psychiatry 28, 923–935.

  • Vanover, K.E. and Barrett, J.E. (1998). An automated learning and memory model in mice: pharmacological and behavioral evaluation of an autoshaped response. Behav. Pharmacol. 9, 273–283. [PubMed]

  • Vasefi, M.S., Yang, K., Li, J., Kruk, J.S., Heikkila, J.J., Jackson, M.F., Macdonald, J.F., and Beazely, M.A. (2013). Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons. Mol. Brain. 6, 24. [Crossref]

  • Vermetten, E. and Lanius, R.A. (2012). Biological and clinical framework for posttraumatic stress disorder. Handb. Clin. Neurol. 106, 291–342. [Crossref] [PubMed]

  • Volk, B., Nagy, B.J., Vas, S., Kostyalik, D., Simig, G., and Bagdy, G. (2010). Medicinal chemistry of 5-HT5A receptor ligands: a receptor subtype with unique therapeutical potential. Curr. Top Med. Chem. 10, 554–578. [Crossref]

  • Wang, Z.Z., Zhang, Y., Liu, Y.Q., Zhao, N., Zhang, Y.Z., Yuan, L., An, L., Li, J., Wang, X.Y., Qin, J.J., et al. (2013). RNA interference-mediated phosphodiesterase 4D splice variants knock-down in the prefrontal cortex produces antidepressant-like and cognition-enhancing effects. Br. J. Pharmacol. 168, 1001–1114.

  • Ward, R.P., Hamblin, M.W., Lachowicz, J.E., Hoffman, B.J., Sibley, D.R., and Dorsa, D.M. (1995). Localization of serotonin subtype 6 receptor messenger RNA in the rat brain by in situ hybridization histochemestry. Neuroscience 64, 1105–1111. [Crossref] [PubMed]

  • Ward, B.O., Wilkinson, L.S., Robbins, T.W., and Everitt, B.J. (1999). Forebrain serotonin depletion facilitates the acquisition and performance of a conditional visual discrimination task in rats. Behav. Brain Res. 100, 51–65. [PubMed] [Crossref]

  • Waters, K.A., Stean, T.O., Hammond, B., Virley, D.J., Upton, N., Kew, J.N., and Hussain, I. (2012). Effects of the selective 5-HT7 receptor antagonist SB-269970 in animal models of psychosis and cognition. Behav. Brain Res. 228, 211–218. [Crossref]

  • Wei, N., Serino, G., and Deng, X.W. (2008). The COP9 signalosome: more than a protease. Trends Biochem. Sci. 33, 592–600. [Crossref]

  • Weiner, M.W., Veitch, D.P., Aisen, P.S., Beckett, L.A., Cairns, N.J., Green, R.C., Harvey, D., Jack, C.R., Jagust, W., Liu, E., et al. (2012). The Alzheimer’s disease neuroimaging initiative: a review of papers published since its inception. Initiative. Alzheimers Dement. 8, S1–68. Epub 2011 Nov 2. [Crossref]

  • West, P.J., Marcy, V.R., Marino, M.J., and Schaffhauser, H. (2009). Activation of the 5-HT6 receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus Neuroscience 164, 692–701.

  • Williams, G.V., Rao, S.G., and Goldman-Rakic, P.S. (2002). The physiological role of 5-HT2A receptors in working memory. J. Neurosci. 22, 2843–2854.

  • Wilson, C. and Terry, A.V. (2009). Enhancing cognition in neurological disorders: potential usefulness of 5-HT6 antagonists. Drug Future 34, 969–975.

  • Witty, D., Ahmed, M., and Chuang, T.T. (2009). Advances in the design of 5-HT6 receptor ligands with therapeutical potential. Progress Med. Chem. 48, 163–225. [Crossref]

  • Woods, S., Clarke, N., Layfield, R., and Fone, K. (2012). 5-HT6 receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br. J. Pharmacol. 167, 436–449.

  • Woolley, M.L., Bentley, J.C., Sleight, A.J., Marsden, C.A., and Fone, K.C. (2001). A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze. Neuropharmacology 41, 210–219. [Crossref]

  • Woolley, M.L., Marsden, C.A., Sleight, A.J., and Fone, K.C. (2003). Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790. Psychopharmacology 170, 358–367. [Crossref]

  • Woolley, M.L., Marsden, C.A., and Fone, K.C. (2004). 5ht6 receptors. Curr Drugs Targets-CNS Neurological Disorders. 3, 59–79.

  • Xu, Y., Yan, J., Zhou, P., Li, J., Gao, H., Xia, Y., and Wang, Q. (2012). Neurotransmitter receptors and cognitive dysfunction in Alzheimer’s disease and Parkinson’s disease. Prog. Neurobiol. 97, 1–13. [PubMed] [Crossref]

  • Youn, J., Misane, I., Eriksson, T.M., Millan, M.J., Ogren, S.O., Verhage, M., and Stiedl, O. (2009). Bidirectional modulation of classical fear conditioning in mice by 5-HT1A receptor ligands with contrasting intrinsic activities. Neuropharmacology 57, 567–576. [Crossref]

  • Yun, H.M. and Rhim, H. (2011a). 5-HT6 receptor ligands, EMD386088 and SB258585, differentially regulate 5-HT6 receptor-independent events. Toxicol. In Vitro 25, 2035–2040.

  • Yun, H.M. and Rhim, H. (2011b). The serotonin-6 receptor as a novel therapeutic target. Exp. Neurobiol. 20, 159–168. [PubMed]

  • Yun, H.M., Kim, S., Kim, H.J., Kostenis, E., Kim, J.I., Seong, J.Y., Baik, J.H., and Rhim, H. (2007). The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn. J. Biol. Chem. 282, 5496–5505.

  • Yun, H.M., Baik, J.H., Kang, I., Jin, C., and Rhim, H. (2010). Physical interaction of Jab1 with human serotonin 6 G-protein-coupled receptor and their possible roles in cell survival. J. Biol. Chem. 285, 10016–10029.

  • Zhang, L., Chang, R.C., Chu, L.W., and Mak, H.K. (2012). Current neuroimaging techniques in Alzheimer’s disease and applications in animal models. Am. J. Nucl. Med. Mol. Imaging 2, 386–404.

  • Zhang, G., Asgeirsdóttir, H.N., Cohen, S.J., Munchow, A.H., Barrera, M.P., and Stackman, R.W. (2013). Current neuroimaging techniques in Alzheimer’s disease and applications in animal models. Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice Neuropharmacology 64, 403–413.

  • Zhou, W., Chen, L., Paul, J., Yang, S., Li, F., Sampson, K., Woodgett, J.R., Beaulieu, J.M., Gamble, K.L., and Li, X. (2012). The effects of glycogen synthase kinase-3beta in serotonin neurons. PLoS One 7, e43262.

  • Zola-Morgan, S. and Squire, L.R. (1993). Neuroanatomy of memory. Ann. Rev. Neurosci. 168, 547–563. [Crossref]

About the article

Alfredo Meneses

Alfredo Meneses received his PhD in Physiological Sciences (1996) from Universidad Nacional Autónoma de Mexico (UNAM). He completed his postdoctoral stay at the NIA, USA from 1997 to 1998. Currently, he is a full Professor at the Department of Pharmacobiology of CINVESTAV. He was invited speaker for the Expert Workshop entitled, ‘Further Understanding of Serotonin 7 Receptors’ Neuropsychopharmacology’ (September 23, 2013, Rome). From 2013 to 2014, he completed two books for Elsevier by invitation, he is an invited editor for the Reviews in the Neuroscience and invited editor for Research Topic as well as associate editor for Frontiers in Pharmacology.

Corresponding author: Alfredo Meneses, Department of Pharmacobiology, CINVESTAV, Tenorios 235, Granjas Coapa, Mexico City 14330, Mexico, e-mail:

Received: 2013-12-03

Accepted: 2014-01-27

Published Online: 2014-04-03

Published in Print: 2014-06-01

Citation Information: Reviews in the Neurosciences, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2014-0001. Export Citation

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