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

作者：Gardier Alain M^*

来源：Behavioural Pharmacology, 2009, 20(1): 18-32.

DOI：10.1097/FBP.0b013e3283243fcd

• antidepressant drugs
• anxiety
• brain-derived neurotrophic factor
• depression
• knockout mouse
• serotonin receptors
• serotonin transporter

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-HT1 B, 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.

• 出版日期2009-2