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 neurotransmission are increasingly used as animal models of depression. In the present study, CVS for 2 weeks and a partial lesion of 5-HT projections by a small dose of parachloroamphetamine (PCA, 2 mg/kg) were applied independently or in combination. CVS reduced significantly the gain in body weight and increased the number of defecations in the open field test. PCA reduced body weight only within the first 24 h after its administration. Consumption of sucrose solution and its preference to water in non-deprived rats were significantly higher in PCA-pretreated rats 2 weeks after CVS compared to control animals. In the forced swimming test, both PCA and CVS treatments reduced immobility on the first but not the second session. Both treatments reduced significantly the time rats spent in social interaction. CVS also elicited an increase in the weight of the right adrenal, but this effect was not present in the PCA-pretreated group. PCA reduced 5-HT and 5-HIAA levels in the frontal cortex, hippocampus, and septum by approximately 20%. CVS increased HVA 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 expected physiological and neurochemical changes, does not reduce sucrose intake or preference in non-deprived animals, but, instead, may increase it after partial 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 social behavior similar to chronic stress.