3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) administration produces dose-dependent neurochemical, endocrine and immune changes in the rat

3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is a widely abused drug t hat is structurally related to both amphetamines and hallucinogens. In addi tion to the behavioural and neurochemical effects of MDMA, we recently repo rted that an acute administration of this drug produces a profound suppress ion of mitogen-stimulated lymphocyte proliferation and reduction in the num ber of circulating white blood cells, which was accompanied by elevated cir culating corticosterone concentrations. In the present study, the effect of acute MDMA administration on PHA-induced lymphocyte proliferation, leucocy te subpopulations, HPA-axis activity and cortical serotonin utilization wer e examined in a dose-dependent manner in female Sprague-Dawley rats. The re sults of this study demonstrate that MDMA induces a suppression of lymphocy te function even at doses that fail to provoke any significant alteration i n central 5-HT utilization and plasma corticosterone concentrations, thereb y suggesting that the reduced functional responsiveness of lymphocytes to m itogenic stimulation after MDMA administration may be mediated by glucocort icoid independent mechanisms. In contrast, the MDMA-induced reduction in th e 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.