國家衛生研究院 NHRI:Item 3990099045/15789
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    题名: Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals
    作者: Chiu, CH;Ma, KH;Huang, EY;Chang, HW;Weng, SJ;Yu, TH;Farn, SS;Kuo, YY;Huang, WS;Cheng, CY;Tao, PL;Yeh, SH
    贡献者: Center for Neuropsychiatric Research
    摘要: BACKGROUND: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. METHODS: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[18F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. RESULTS: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. CONCLUSION: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[18F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.
    日期: 2024-05
    關聯: Journal of the Chinese Medical Association. 2024 May 1;87(5):538-549.
    Link to: http://dx.doi.org/10.1097/jcma.0000000000001087
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1726-4901&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001275697500006
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85193055189
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