Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA either once (acute) or for 20 days (chronic) and were euthanized 7 days following the last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone concentrations, and serum testosterone levels as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the hypothalamic-pituitary-gonadal axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. (c) 2008 S. Karger AG, Basel.