Differences in neurochemical response to immobilization stress were measured in rats given a neurotoxic regimen 4 i.p. injections of 10 mg/kg MDMA or saline, with treatments given once every 2 h. 5-HT and DA were measured via microdialysis probes placed in the pre-frontal cortex (5-HT, DA) and the dorsal hippocampus (5-HT only). Corticosterone response after MDMA was measured in blood taken from a separate group of rats that were either killed immediately after MDMA or saline treatment, or 1 wk after MDMA or saline, with some receiving immobilization before sacrifice. 5-HT was significantly reduced in dorsal hippocampus after MDMA, but there was no change in basal pre-frontal 5-HT or pre-frontal DA after MDMA treatment. While saline-treated rats had significantly increased extracellular 5-HT in pre-frontal cortex and hippocampus 40 min post-stress, MDMA-treated rats did not have increased hippocampal 5-HT at this time. Pre-frontal DA also increased after immobilization stress in saline-treated, but not MDMA-treated, rats. MDMA-treated and saline-treated rats did not differ in basal corticosterone concentrations, and corticosterone increased in both groups after immobilization stress. The authors hypothesize that decreased pre-frontal DA after immobilization stress in MDMA-treated animals could either arise from less 5-HT-mediated inhibition of GABAergic tone on DA neurons, or through attenuated stress-induced release of 5-HT. The authors explain the lack of attenuated corticosterone response in MDMA-treated rats as an indicator of the selectivity of 5-HT neurotoxicity, with cortical and limbic pathways more affected than hypothalamic ones. In contrast with findings reported here, ecstasy users appeared to release more cortisol in response to a potentially stressful situation (competing for points with monetary value) (Gerra et al. 2001), but ecstasy users also responded more aggressively, and so the increased cortisol may have been behaviorally mediated in this case.