The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness

Jaime M. Monti 1  and Héctor Jantos 1
  • 1 Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11600, Uruguay
Jaime M. Monti
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  • Jaime M. Monti is Professor in the Department of Pharmacology and Therapeutics at the University of the Republic School of Medicine (Montevideo, Uruguay). He received his postdoctoral training at Stanford University School of Medicine (CA, USA). He has published over 150 peer-reviewed articles and book chapters on sleep research topics. His primary research interests include insomnia, and the experimental and clinical pharmacology of sleep.
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and Héctor Jantos
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  • Héctor Jantos is Assistant of Research in the Department of Pharmacology and Therapeutics at the University of the Republic School of Medicine (Montevideo, Uruguay). He has published over 50 peer-reviewed articles on the preclinical pharmacology of sleep. His primary research interests include the role of monoamines (serotonin, dopamine, histamine) and peptides (melanin concentrating hormone) in the regulation of the behavioral states.
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Abstract

Different approaches have been followed to characterize the role of 5-hydroxytryptamine (serotonin) receptor 7 (5-HT7) in the regulation of sleep-wake behavior: (1) 5-HT7 receptor knockout mice spend less time in rapid eye movement sleep than their wild-type counterparts, mainly during the light period. In contrast, there is no difference between the genotypes in time spent in wakefulness or slow-wave sleep. (2) Systemic administration of the selective 5-HT7 receptor agonist LP-211 significantly increased wakefulness (time spent awake) and reduced rapid eye movement sleep in the rat. Direct infusion of LP-211 into the dorsal raphe nucleus, locus coeruleus nucleus, basal forebrain (horizontal limb of the diagonal band of Broca), or laterodorsal tegmental nucleus also produced a decrease in rapid eye movement sleep. Additionally, microinjection of the 5-HT7 receptor agonist into the basal forebrain augmented the time animals remained awake. Local injection of the 5-HT7 receptor agonist LP-44 into the dorsal raphe nucleus also suppressed rapid eye movement sleep in the rat. (3) A similar reduction of rapid eye movement sleep has been described following intraperitoneal injection of the selective 5-HT7 receptor antagonists SB-269970 and SB-656104 in the rat and oral administration of the 5-HT7 receptor antagonist NJ-18038683 to rat and man. Local microinjection of SB-269970 into the dorsal raphe nucleus and basal forebrain also induced a decrease in rapid eye movement sleep in the rat. This tends to suggest that the on-off (activation/blockade), two-state ligand-receptor interaction model is not tenable for the 5-HT7 receptor.

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