Endocrine and neurochemical effects of S(+) and R(‐)‐MDMA in rhesus macaques

Abstract

3,4‐Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that produces complex subjective effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two isomers that exhibit qualitatively different effects. In particular, drug discrimination studies in rodents have shown that R(‐)‐MDMA tends to have hallucinogen‐like effects whereas S(+)‐MDMA tends to have stimulant‐like effects. However, relatively little work has shown that these qualitative differences extend across taxa. In the present study, the neurochemical and endocrine effects of each isomer were assessed in rhesus macaques after non‐contingent intravenous delivery of each isomer. Specifically, in vivo microdialysis was utilized to assess extracellular concentrations of dopamine in the dorsal striatum and plasma concentrations of prolactin were assessed to determine the systemic effect of each isomer on dopamine and serotonin overflow. Only S(+)‐MDMA significantly increased dopamine concentration, and it produced a blunted increase in prolactin levels compared to R(‐)‐MDMA. These studies demonstrate that qualitative differences in the effects of the isomers of MDMA extend to primates; strengthening the inference that this may be the mechanism producing the complex subjective effects of MDMA in humans. These studies were supported by USPHS grants (DA 10344, DA 00517, and RR 00165).