Hatzidimitriou G, Tsai EH, McCann UD, Ricaurte GA (2002). Altered prolactin response to M-chlorophenylpiperazine in monkeys previously treated with 3,4-methylenedioxymethamphetamine (MDMA) or fenfluramine. Synapse 44: 51-57. Neurotoxicity, 4/02
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The serotonin-releasing agent mCPP (2.5 mg/kg) was administered to squirrel monkeys given a neurotoxic regimen of MDMA (5 mg/kg twice daily for 4 days) or fenfluramine (same regimen) either 2 wks previous to challenge, 2 years previously (d-fenfluramine) or 3.5 years prior to challenge (MDMA). A baseline challenge with mCPP was performed 2 wks before MDMA or fenfluramine regimen for all monkeys, and response to baseline challenge was used to match monkeys in each condition on neuroendocrine response to mCPP. (Challenge was performed on anesthetized animals). Monkeys treated 2 wks previously with MDMA showed a trend for lower prolactin response after mCPP compared with controls, but prolactin was significantly elevated in monkeys given MDMA 3.5 years previously and monkeys given d-fenfluramine 2 years previously. Cortisol response to mCPP varied greatly, and there were no significant differences in cortisol response to mCPP between any of the treatment groups, including both MDMA treatment groups. The authors describe their results as supporting MDMA-induced neurotoxicity at 2 weeks after MDMA, and signs of reinnervation 3.5 years after MDMA (and 2 years after d-fenfluramine). Examinations of neuroendocrine response after mCPP performed by the same team (McCann et al. 1999) found blunted prolactin response in male ecstasy users when compared with controls; time since last use of ecstasy in this sample was approximately 3 months. Taken together, study findings form the human and monkey studies either suggests that humans take longer for neuroendocrine responses to return to normal values, or that MDMA-induced changes in response to mCPP are not comparable across species. It is also possible that elevated prolactin response to mCPP in MDMA-treated animals at 3.5 years is due to pre-existing variance in prolactin, since baseline prolactin measures were not performed at the later point in time. These results also suggest that MDMA and d-fenfluramine have similar effects on squirrel monkey neuroendocrine response to mCPP.

 
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