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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board Member: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Eichenbaum, Howard / Gold, Paul / Holsboer, Florian / Korth, Carsten / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

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2191-0200
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Volume 23, Issue 4 (Aug 2012)

Issues

Characterization of serotonin neurotransmission in knockout mice: implications for major depression

Sergio Domínguez-López
  • Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West Room 220, Montreal H3A 1A1, Quebec, Canada
  • Other articles by this author:
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/ Rebecca Howell
  • Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West Room 220, Montreal H3A 1A1, Quebec, Canada
  • Other articles by this author:
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/ Gabriella Gobbi
  • Corresponding author
  • Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West Room 220, Montreal H3A 1A1, Quebec, Canada
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  • Other articles by this author:
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Abstract

The interaction between genes and environment plays a significant role in the pathogenesis of major depression and mood disorders. Preclinical and clinical studies have established that a dysfunction of serotonin (5-HT) neurotransmission is a common hallmark in major depression and drugs acting on the 5-HT system have antidepressant properties. In the past 15 years, the development of knockout mice showing a depressive-like or resilience-like phenotype have allowed us to better understand the complex relationship between genes, behaviour and the 5-HT system in mood disorders. The present review revises several knockout mice genotypes with ‘mood’ alteration and analyses how 5-HT firing activity, measured with electrophysiological techniques, is impaired after a gene manipulation. The behavior and electrophysiology data from 5-HT transporter (5HTT), 5-HT1A, 5-HT4, the neurokinin 1 (NK1) receptor, fatty acid amide hydrolase (FAAH) and the TWIK-1 related K+ (TREK-1) channel knockout mice are here analysed. Interestingly, a correlation between 5-HT firing rate and depressive/resilience phenotypes can be established in these different knockouts. Furthermore, findings in knockout mice have been successfully translated to humans, and findings from human studies have helped to design and generate knockout mice to explore new hypotheses of the etiology of human depression. The correlation of 5-HT activity and behavior could be a predictor factor for understanding the role of receptors, channels and enzymes in depression, and could be used also to assess the potential antidepressive effects of novel drugs.

Keywords: behavioral phenotype; depression; knockout mouse; neurotransmission; serotonin; translational studies

About the article

Corresponding author: Gabriella Gobbi, MD, PhD, Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West Room 220, Montreal H3A 1A1, Quebec, Canada


Published in Print: 2012-08-01


Citation Information: , ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2012-0044.

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©2012 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

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