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

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


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.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Depressive Disorder / drug therapy*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Knockout / genetics*
  • Mice, Knockout / psychology
  • Models, Animal*
  • Polymorphism, Genetic / drug effects
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1 / genetics
  • Receptors, Serotonin, 5-HT4 / genetics
  • Serotonin / genetics*
  • Serotonin / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / genetics


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Plasma Membrane Transport Proteins
  • Receptors, Serotonin, 5-HT4
  • Serotonin
  • Receptor, trkB