WATER SWIM STRESS
3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely abused drug that is structurally related to both amphetamines and hallucinogens. In addition to the behavioural and neurochemical effects of MDMA, we recently reported that an acute administration of this drug produces a profound suppression of mitogen-stimulated lymphocyte proliferation and reduction in the number of circulating white blood cells, which was accompanied by elevated circulating corticosterone concentrations. In the present study, the effect of acute MDMA administration on PHA-induced lymphocyte proliferation, leucocyte subpopulations, HPA-axis activity and cortical serotonin utilization were examined in a dose-dependent manner in female Sprague-Dawley rats. The results of this study demonstrate that MDMA induces a suppression of lymphocyte function even at doses that fail to provoke any significant alteration in central 5-HT utilization and plasma corticosterone concentrations, thereby suggesting that the reduced functional responsiveness of lymphocytes to mitogenic stimulation after MDMA administration may be mediated by glucocorticoid independent mechanisms. In contrast, the MDMA-induced reduction in the number of circulating blood lymphocytes was evident only at doses of MDMA which elevated circulating corticosterone concentrations, suggesting that the observed reduction in circulating lymphocytes may be at least partly a glucocorticoid-mediated event. Copyright (C) 1999 John Wiley & Sons, Ltd.