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    题名: Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice
    作者: 詹銘煥
    Chiu, Hong-Yi;Chan, Ming-Huan;Lee, Mei-Yi;Chen, Shao-Tsu;Zhan, Zih-Yi;Chen, Hwei-Hsien
    贡献者: 神科所
    关键词: 5-HT2A receptor;methamphetamine;psychosis
    日期: 2014-10
    上传时间: 2015-02-10 18:04:01 (UTC+8)
    摘要: The repeated administration of methamphetamine (MA) to animals in a single-day ‘binge’ dosing regimen produces damage to dopamine and serotonin terminals and psychosis-like behaviours similar to those observed in MA abusers. The present study aimed to examine the effects of MA binge exposure on 5-HT2A receptors, the subtype of serotonin receptors putatively involved in psychosis. ICR male mice were treated with MA (4 × 5 mg/kg) or saline at 2 h intervals. Recognition memory and social behaviours were sequentially evaluated by a novel location recognition test, a novel object recognition test, a social interaction and a nest-building test to confirm the persistent cognitive and behavioural impairments after this dosing regimen. Subsequently, a hallucinogenic 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch, molecular and electrophysiological responses were monitored. Finally, the levels of 5-HT2C, 5-HT1A, 5-HT2A and mGlu2 receptors in the medial prefrontal cortex were determined. MA binge exposure produced recognition memory impairment, reduced social behaviours, and increased DOI-induced head-twitch response, c-Fos and Egr-2 expression and field potentials in the medial prefrontal cortex. Furthermore, MA binge exposure increased 5-HT2A and decreased mGlu2 receptor expression in the medial frontal cortex, whereas 5-HT2C and 5-HT1A receptors were unaffected. These data reveal that the increased behavioural, molecular and electrophysiological responses to DOI might be associated with an up-regulation of 5-HT2A receptors in the medial prefrontal cortex after MA binge exposure. Identifying the biochemical alterations that parallel the behavioural changes in a mouse model of MA binge exposure may facilitate targeting therapies for treatment of MA-related psychiatric disorders.
    關聯: International Journal of Neuropsychopharmacology, 17(10), 1647-1658
    数据类型: article
    DOI 連結: http://dx.doi.org/10.1017/S1461145714000455
    DOI: 10.1017/S1461145714000455
    显示于类别:[神經科學研究所 ] 期刊論文

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