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Behav Pharmacol. 2009 Feb;20(1):18-32. doi: 10.1097/FBP.0b013e3283243fcd.

Mutant mouse models and antidepressant drug research: focus on serotonin and brain-derived neurotrophic factor.

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University Paris-Sud, EA 3544 Faculty of Pharmacy, Chatenay-Malabry Cedex, France.


Several lines of knockout (KO) mice have been evaluated as models of depression-related behavioral and neurobiological changes, and used to investigate molecular and cellular mechanisms underlying the activity of antidepressant drugs. Adult neurogenesis and brain 5-hydroxytryptamine (5-HT)/neurotrophic factor interactions have recently attracted great interest in relation to the mechanism of action of antidepressant drugs. The present review focuses primarily on genetic manipulation of the serotoninergic (5-HT) system. Basal neurochemical and behavioral changes occurring in mice lacking the 5-HT transporter (SERT), which is the main target of antidepressant drugs, as well as in those lacking G protein-coupled serotonin receptors (e.g. 5-HT1B, 5-HT1A, and 5-HT4 receptors) are described and evaluated. The importance of KO mice for neurotrophic factors, particularly for brain-derived neurotrophic factor and its high-affinity receptor (R-TrkB), is also addressed. Constitutive KO, tissue specific, or inducible KO mice targeting both 5-HT and brain-derived neurotrophic factor systems may potentially make an important contribution to knowledge of the pathophysiology and treatment of depression.

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