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Sex-related differential response to clomipramine treatment in a rat model of depression

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece

K. Antoniou

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece, Department of Pharmacology, Medical School, University of Ioannina, Greece

C. Dalla

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece, Department of Psychology, Rutgers University, New Jersey, USA

S. Bekris

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece

M. Xagoraris

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece

DH Ovestreet

Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapell Hill, NC, USA

Z. Papadopoulou-Daifoti

Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece, zdaifoti{at}med.uoa.gr

Research in affective disorders is often performed without considering sex differences, although women are predominantly affected. Consequently, the potential sex-dependent action of antidepressants remains elusive. We investigated whether Flinders sensitive line (FSL) of rats, a model of depression, would present sex-differentiated responses to antidepressant treatment. FSL and Sprague—Dawley rats were treated with clomipramine 10 mg/kg/day for 14 days. Subsequently, they were subjected to either a single session of the forced swim test or an estimation of serotonergic function in the prefrontal cortex, hippocampus, amygdala and hypothalamus. Male FSL displayed increased immobility duration, decreased active behaviours, increased serotonin tissue levels and a reduced serotonin turnover rate in most brain areas studied. Female FSL showed a distinct profile, consisting of decreased immobility latency, increased climbing duration, limited serotonergic deviations and no difference in the serotonin turnover rate in comparison with controls. Interestingly, despite baseline differences, clomipramine treatment reversed all relevant behavioural responses and increased the serotonin turnover rate in both sexes. However, the latter effect was remarkably more pronounced in females. It is concluded that, in this animal model of depression, chronic clomipramine treatment attenuated baseline sex differences in the phenotype while maintaining or intensifying the sex differentiation in the serotonergic endophenotype.

Key Words: antidepressants • depression • female rats • Flinders sensitive line of rats • forced swim test • serotonin • sex differences

This version was published on November 1, 2009

Journal of Psychopharmacology, Vol. 23, No. 8, 945-956 (2009)
DOI: 10.1177/0269881108095914


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