Chronic variable stress and partial 5-HT denervation by parachloroamphetamine treatment in the rat: effects on behavior and monoamine neurochemistry

Chronic variable stress (CVS) and manipulations of 5-HT-ergic neurotransmis sion are increasingly used as animal models of depression. In the present s tudy, CVS for 2 weeks and a partial lesion of 5-HT projections by a small d ose of parachloroamphetamine (PCA, 2 mg/kg) were applied independently or i n combination. CVS reduced significantly the gain in body weight and increa sed the number of defecations in the open field test. PCA reduced body weig ht only within the first 24 h after its administration. Consumption of sucr ose solution and its preference to water in non-deprived rats were signific antly higher in PCA-pretreated rats 2 weeks after CVS compared to control a nimals. In the forced swimming test, both PCA and CVS treatments reduced im mobility on the first but not the second session. Both treatments reduced s ignificantly the time rats spent in social interaction. CVS also elicited a n increase in the weight of the right adrenal, but this effect was not pres ent in the PCA-pretreated group. PCA reduced 5-HT and 5-HIAA levels in the frontal cortex, hippocampus, and septum by similar to 20%. CVS increased HV A levels in the frontal cortex. Applied together, PCA pretreatment and CVS increased dopamine turnover in the frontal cortex. Conclusively, this study has provided evidence that chronic variable stress, which elicited expecte d physiological and neurochemical changes, does not reduce sucrose intake o r preference in non-deprived animals, but, instead, may increase it after p artial 5-HT-ergic denervation; and that partial 5-HT-ergic denervation by a low dose PCA treatment has a long-lasting effect on forced swimming and so cial behavior similar to chronic stress. (C) 2001 Elsevier Science B.V. All rights reserved.