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Effects of a short-course MDMA binge on dopamine transporter binding and on levels of dopamine and its metabolites in adult male rats

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Dominik K. Biezonski, Brian J. Piper, Nina M. Shinday, Peter J. Kim, Syed F. Ali, Jerrold S. Meyer
European Journal of Pharmacology, Volume 701, Issues 1–3, 15 February 2013

Abstract

Although the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is often described as a selective serotonergic neurotoxin, some research has challenged this view. The objective of this study was to determine the influence of MDMA on subsequent levels of two different markers of dopaminergic function, the dopamine transporter (DAT) as well as dopamine and its major metabolites. In experiment I, adult male Sprague–Dawley rats were administered either a low or moderate dose MDMA binge (2.5 or 5.0 mg/kg×4 with an inter-dose interval of 1 h) or saline, and were killed 1 week later. The moderate dose dramatically reduced [3H]WIN 35,428 binding to striatal DAT by 73.7% (P≤0.001). In experiment II, animals were binged with a higher dose of MDMA (10 mg/kg×4) to determine the drug’s effects on concentrations of serotonin (5-HT), dopamine, and their respective major metabolites 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum and frontal cortex 1 week later. As expected, MDMA significantly reduced 5-HT and 5-HIAA (≥50%) in these structures, while only a marginal decrease in dopamine was noted in the striatum. In contrast, levels of DOPAC (34.3%, P<0.01) and HVA (33.5%, P<0.001) were reduced by MDMA treatment, suggesting a decrease in dopamine turnover. Overall, these findings indicate that while serotonergic markers are particularly vulnerable to MDMA-induced depletion, significant dopaminergic deficits may also occur under some conditions. Importantly, DAT expression may be more vulnerable to perturbation by MDMA than dopamine itself.

Copyright © 2013 Elsevier B.V.

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Additional Information:

MDMA, better known as ecstasy, is a popular recreational drug that has also been studied as an agent that could be used with psychotherapy to treat Post Traumatic Stress Disorder. MDMA is well known as a serotonin neurotoxin in animal studies as well as in humans but less is known about other neurotransmitter systems. This study found that MDMA, using a multiple dose regimen that more closely approximates the timing used by humans than was employed in prior research, reduces the levels of the dopamine transporter, a protein found on the axons of dopamine neurons, in rats. This finding is important because dopamine is integral for emotion, reward, and movement for diseases like Parkinson’s. This report has clear public health implications for individuals considering experimenting with this drug.