5-HT4 Receptor Subtype- ?-Arrestin Level- and Rapid-Onset Effects of Antidepressant Drugs

Authors
Indira Mendez-David, Denis Joseph David, Jean-Philippe Guilloux, René Hen, Alain Michel Gardier

Lab
Universität zu Köln

Journal
Neuromethods Volume 95

Abstract
Understanding the pathophysiology of affective disorders and their treatment relies on the availability of experimental models that accurately mimic aspects of the disease. The use of exogenously administered corticosterone (CORT model) can mimic the effects of a chronic stress and has been validated as an animal model to study disease states displaying some hallmark characteristics of anxiety and depression observed in patients.Recently, we have adapted the CORT model protocol to screen for rapid-onset drugs to treat anxiety/depression disorders. In spite of the fact that selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for the treatment of depression and several anxiety disorders, the onset of action of SSRIs is often delayed by 3–6 weeks. The existence of this delayed action combined with the fact that one-third of patients do not respond to treatment emphasizes the need for faster acting and more effective antidepressants. This chapter gives laboratory protocols including step-by-step recommendations to explain how the CORT model in mice can be used to screen for candidate drugs. For this purpose we examined the behavioral and cellular effects of a 5-HT4 receptor ligand, RS67333, and compared it with the SSRI, fluoxetine. Likewise, we emphasize that mononuclear cells (PBMCs) isolated from whole blood in corticosterone-treated mice could serve as a marker of treatment response(s) and fast onset of drug action in the mouse CORT model.

BIOSEB Instruments Used:
Elevated Plus Maze : EPM3C - 3 clicks only ! (BIO-EPM3C)