Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(−)-MDMA tends to have hallucinogen-like effects, whereas S(+)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether these stereoisomers engender different endocrine and neurochemical effects. In the present study, the endocrine and neurochemical effects of each stereoisomer and the racemate were assessed in four rhesus monkeys after intravenous delivery at doses (1–3 mg/kg) that approximated voluntary self-administration by rhesus monkeys and human recreational users. Specifically, fluorescence-based enzyme-linked immunosorbent assay was used to assess plasma prolactin concentrations, and in vivo microdialysis was used to assess extracellular dopamine and serotonin concentrations in the dorsal striatum. R(−)-MDMA, but not S(+)-MDMA, significantly increased plasma prolactin levels and the effects of S,R(±)-MDMA were intermediate to each of its component stereoisomers. Although S(+)-MDMA did not alter prolactin levels, it did significantly increase extracellular serotonin concentrations. In addition, S(+)-MDMA, but not R(−)-MDMA, significantly increased dopamine concentrations. Furthermore, as in the prolactin experiment, the effects of the racemate were intermediate to each of the stereoisomers. These studies demonstrate the stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomers might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.
Footnotes
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This work was supported by the National Institutes of Health [Grants DA15040, DA020645, RR020146, DA10344, DA00517, RR00165].
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Preliminary findings from these experiments were previously presented: Murnane KS (2009) Endocrine and neurochemical effects of S(+) and R(-)-MDMA in rhesus macaques, 2009 Experimental Biology Meeting; 2009, April 18–22; New Orleans, LA. American Physiological Society, Bethesda, MD.
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These studies represent partial fulfillment of K.S.M.'s dissertation research at Emory University.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.166595.
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ABBREVIATIONS:
- MDMA
- 3,4-methylenedioxymethamphetamine
- DOPAC
- 3,4-dihydroxyphenylacetic acid
- HVA
- homovanillic acid
- mCPP
- meta-chlorophenylpiperazine
- HPLC
- high-performance liquid chromatography
- RM
- repeated measures
- ANOVA
- analysis of variance
- 5-HT
- 5-hydroxytryptamine
- Received January 27, 2010.
- Accepted May 12, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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