FORCED SWIM TEST-INDUCED NEUROCHEMICAL, ENDOCRINE, AND IMMUNE CHANGESIN THE RAT

The forced swim test (FST) is a behavioral paradigm that is widely use d as a screening test for antidepressant activity in rodents. The obje ctives of the present study were to characterize the corticosterone an d immune responses and in addition to examine neurotransmitter levels, in five brain regions at intervals (15, 30, 60, 90, and 120 min) foll owing the second exposure to the FST. There was a significant but tran sient reduction in noradrenaline and 5-HT concentrations, in the hypot halamus 15 min post-FST exposure. 5-HT turnover in the frontal cortex and amygdala was significantly increased between 20-120 min post-FST e xposure. The FST elicited a robust corticosterone response that peaked significantly at 30 min and had almost returned to baseline 120 min a fter exposure. There was a significant reduction in total white blood cell count 120 min after the FST, which was accompanied by a sig nific antly reduced percentage of lymphocytes 90 and 120 min post-FST exposu re. In addition, there was a significant but transient suppression of both PHA and Con A-induced lymphocyte proliferation 15 min following F ST exposure. This study demonstrates that there are neurochemical chan ges that are coincident with the endocrine and immune changes associat ed with FST exposure in rats. Furthermore, this model could be used to examine the effects of manipulation of this stress response by antide pressant drugs. Such an investigation could add to our understanding o f the interactions between antidepressants,stress and the neuroendocri ne and immune systems. (C) 1997 Elsevier Science Inc.