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Pharmacological validation of a chronic social stress model of depression in rats: effects of reboxetine, haloperidol and diazepam.

Rygula R, Abumaria N, Havemann-Reinecke U, Rüther E, Hiemke C, Zernig G, Fuchs E, Flügge G

Departments of aPsychiatry and Psychotherapy bNeurology, University of Göttingen cClinical Neurobiology Laboratory, German Primate Center dCenter for the Molecular Physiology of the Brain, Göttingen eDepartment of Psychiatry, University of Mainz, Germany fDepartment of Psychiatry, Medical University Innsbruck, Austria.

Chronic social stress is one of the most important factors responsible for precipitation of depressive disorder in humans. In recent years, the impact of social stress on the development of psychopathologies has been thoroughly investigated in preclinical animal studies. We have shown recently that behavioural effects of chronic social stress in rats can be reversed by citalopram and fluoxetine. This study has been designed for further pharmacological validation of the chronic social stress paradigm as a model of depressive symptoms in rats. For this, rats were subjected to 5 weeks of daily social defeat and were in parallel treatment for a clinically relevant period of 4 weeks with the antidepressant drug reboxetine (40 mg/kg/day) and the neuroleptic drug haloperidol (2 mg/kg/day). The anxiolytic diazepam (1 mg/kg) was administered acutely at the end of the stress period. Stress caused decreased locomotor and exploratory behaviours, decreased sucrose preference and increased immobility in the forced swim test, but did not affect behaviour in the elevated plus maze. Four weeks of oral treatment with reboxetine ameliorated the adverse effects of social stress and normalized behaviours related to motivation and reward sensitivity. The treatment with haloperidol worsened the adverse effects of chronic social stress having effects similar to stress on reward and motivation-related behaviours. Diazepam reduced anxiety-related behaviours as measured in elevated plus maze in control animals having no effects on socially stressed individuals. Neither sucrose preference nor performance in forced swim test was affected by diazepam. The effectiveness and selectivity of the treatment with the antidepressant reboxetine in ameliorating socially induced behavioural disturbances supports the validity of the chronic social stress as a model of depressive-like symptoms in rats.

Published 12 May 2008 in Behav Pharmacol, 19(3): 183-196.
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