Citalopram counteracts depressive-like symptoms evoked by... : Behavioural Pharmacology (original) (raw)
ORIGINAL ARTICLES
Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats
Rygula, Rafala b *; Abumaria, Nashatb *; Flügge, Gabrieleb; Hiemke, Christophc; Fuchs, Eberhardb d; Rüther, Eckarta; Havemann-Reinecke, Ursulaa
aDepartment of Psychiatry and Psychotherapy, University of Göttingen
bClinical Neurobiology Laboratory, German Primate Center, Göttingen
cDepartment of Psychiatry, University of Mainz
dDepartment of Neurology, University of Göttingen, Germany
Correspondence and requests for reprints to Rafal Rygula, Department of Psychiatry and Psychotherapy, University of Göttingen, von Sieboldstr. 5, D-37075 Göttingen, Germany
E-mail: [email protected]
Received 30 June 2005 Accepted as revised 26 October 2005
*These authors contributed equally to this work.
Abstract
Recently, we have described a new model of chronic social stress in rats, based on the resident–intruder paradigm. In this model, rats show behavioural changes that may be considered correlates of depressive symptoms, such as anhedonia and motivational deficits. The present study was designed for pharmacological validation of this model. Animals were socially stressed for 5 weeks and, in parallel, after the first week of stress, they were subjected to chronic (4 weeks) treatment with the antidepressant drug citalopram. The drug was administered via drinking water (30 mg/kg). The optimal dose of citalopram was determined in a pilot study. After 4 weeks of treatment, plasma levels of citalopram and its metabolite were found to be within the human therapeutic range. The effects of social stress and citalopram treatment were assessed by behavioural tests. Chronically stressed rats showed reduced locomotor and exploratory activity, reduced sucrose preference and increased immobility time in the forced swimming test. Chronic oral administration of citalopram abolished those effects and normalized behaviours related to motivation and reward sensitivity. These observations provide evidence for the predictive validity of the chronic social stress paradigm as a model of depressive symptoms in rats.
© 2006 Lippincott Williams & Wilkins, Inc.