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Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT.

Kuo-Hsing Ma, Tsung-Ta Liu, Shao-Ju Weng, Chien-Fu F Chen, Yuahn-Sieh Huang, Sheau-Huei Chueh, Mei-Hsiu Liao, Kang-Wei Chang, Chi-Chang Sung, Te-Hung Hsu, Wen-Sheng Huang, Cheng-Yi Cheng

Scientific Reports December 12, 2016 DOI: 10.1038/srep38695 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 9
Population Monkeys (Macaca cyclopis)
Interventions MDMA Dextromethorphan
Duration Over four years
Measures [123I]-ADAM uptake ratios (SPECT)
Topics Serotonin MDMA
Keywords Brain Animals Primates Iodine radioisotopes N-methyl-3,4-methylenedioxyamphetamine Cinanserin Dextromethorphan Tomography, emission-computed, single-photon Magnetic resonance imaging Time factors
Key findings MDMA-treated monkeys showed significantly lower brain SERT levels than controls, as measured by [123I]-ADAM uptake ratios, and this decrease persisted for over four years. Co-treatment with dextromethorphan appeared to prevent the SERT loss, suggesting a possible protective effect against MDMA-induced serotonergic toxicity.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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