Effect of subchronic antidepressant treatments on behavioral, neurochemical, and endocrine changes in the forced-swim test

The purpose of the present study was to examine the effect of subchronic tr eatment (24 days) with antidepressants displaying differential effects on n oradrenaline and serotonin reuptake, on behavior, neurochemistry and hypoth alamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IF) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IF) and venlafaxine (10 mg/kg, IF) were w ithout effect. Nonetheless, treatment with all three antidepressants signif icantly attenuated stress-related increases in amygdaloid and cortical sero tonin turnover. Of the three antidepressants examined, only desipramine att enuated the stress-associated elevation in serum corticosterone. In conclus ion, although FST-induced increases in serotonin turnover in the frontal co rtex and amygdala were attenuated following treatment with all three antide pressants, FST-induced behavioral changes and increased HPA axis activity w ere normalized only following desipramine treatment. In addition, these res ults suggest that neurochemical mechanisms independent of increased seroton ergic activity subserve the normalization of behavior and HPA axis response s in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and e ndocrine alterations, and illustrates important differences between classes of antidepressants. (C) 2000 Elsevier Science Inc.