Interest of using genetically manipulated mice as models of depression to evaluate antidepressant drugs activity: a review.

Publisher: Blackwell Science Country of Publication: England NLM ID: 8710411 Publication Model: Print Cited Medium: Internet ISSN: 1472-8206 (Electronic) Linking ISSN: 07673981 NLM ISO Abbreviation: Fundam Clin Pharmacol Subsets: MEDLINE

Publication: <2001->: Oxford : Blackwell Science
Original Publication: Paris ; New York : Elsevier, c1987-

Disease Models, Animal*; Antidepressive Agents/*pharmacology ; Depressive Disorder/*drug therapy; Animals ; Behavior, Animal/drug effects ; Brain-Derived Neurotrophic Factor/genetics ; Depressive Disorder/physiopathology ; Drug Delivery Systems ; Drug Evaluation, Preclinical/methods ; Humans ; Mice ; Mice, Knockout ; Receptors, G-Protein-Coupled/genetics ; Serotonin Plasma Membrane Transport Proteins/genetics

Among the multiple possibilities to study human depressive disorders, animal models remain important preclinical tools. They allow the understanding of the mechanisms of action of antidepressant drugs. Primarily developed in rat, animal models of depression have been adapted to the mouse, an easy-to-use mammal with better genetic possibilities than rats. As an example, genetic manipulation of the serotoninergic 5-hydroxytryptamine-HT; (5-HT) system provided important opportunities to investigate the role of this monoamine in mood disorders. The contribution of either constitutive knockout (KO), tissue specific, or inducible KO mice and animal models in the current knowledge of the pathophysiology and treatment of depression is unanimously recognized. The phenotype of genetically manipulated animals is strongly influenced by both the genetic background of the animal as well as environmental factors. For these reasons, it is necessary to underline that KO mice have been generated on various genetic backgrounds, which strongly influence the behavioral and neurochemical responses to the tests. The present review will thus focus on KO mice lacking G protein-coupled monoaminergic receptors (e.g; 5-HT1B, 5-HT1A, and 5-HT4 receptors) and the 5-HT serotonin transporter, which is the main target of antidepressant drugs (or strategies). The importance of KO mice for neurotrophic factors, particularly for brain-derived neurotrophic factor and its main receptor displaying a tyrosine kinase activity, will also be addressed to illustrate the fact that in preclinical studies, combination of genetic manipulations with pharmacological ones should allow further progress in the field of neuropsychopharmacology.

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0 (Antidepressive Agents)
0 (Brain-Derived Neurotrophic Factor)
0 (Receptors, G-Protein-Coupled)
0 (Serotonin Plasma Membrane Transport Proteins)

Date Created: 20090310 Date Completed: 20090601 Latest Revision: 20090309

20240829

10.1111/j.1472-8206.2008.00640.x

19267769