Mutant mouse models and antidepressant drug research: focus on serotonin and brain-derived neurotrophic factor.
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.
Gardier
Alain M
AM
University Paris-Sud, EA 3544 Faculty of Pharmacy, Chatenay-Malabry Cedex, France. alain.gardier@u-psud.fr
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics* / Q000523:psychology; D023421:Models, Animal; D011110:Polymorphism, Genetic / Q000187:drug effects; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000235:genetics; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics; D012701:Serotonin / Q000235:genetics* / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D020813:Receptor, trkB