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). [ 123 I]-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 [ 123 I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [ 123 I]-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.
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Ma, K. H., Liu, T. T., Weng, S. J., Chen, C. F. F., Huang, Y. S., Chueh, S. H., Liao, M. H., Chang, K. W., Sung, C. C., Hsu, T. H., Huang, W. S., & Cheng, C. Y. (2016). Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [ 123 I]-ADAM/SPECT. Scientific Reports, 6, . https://doi.org/10.1038/srep38695