title: Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT.
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.
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tsung-Ta
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Weng
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Fu F
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yuahn-Sieh
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sheau-Huei
authors.initials: SH
authors.lastname: Chueh
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Mei-Hsiu
authors.initials: MH
authors.lastname: Liao
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Chang
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Sung
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Te-Hung
authors.initials: TH
authors.lastname: Hsu
authors.affiliation: Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002928:Cinanserin / Q000031:analogs & derivatives*; D003915:Dextromethorphan / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011323:Primates; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D007457:Iodine Radioisotopes; D012701:Serotonin; D003915:Dextromethorphan; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D002928:Cinanserin