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題名 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
貢獻者 神科所
關鍵詞 5-HT2A receptor;methamphetamine;psychosis
日期 2014-10
上傳時間 10-二月-2015 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
資料類型 article
DOI http://dx.doi.org/10.1017/S1461145714000455
dc.contributor 神科所
dc.creator (作者) 詹銘煥zh_TW
dc.creator (作者) Chiu, Hong-Yi;Chan, Ming-Huan;Lee, Mei-Yi;Chen, Shao-Tsu;Zhan, Zih-Yi;Chen, Hwei-Hsien
dc.date (日期) 2014-10
dc.date.accessioned 10-二月-2015 18:04:01 (UTC+8)-
dc.date.available 10-二月-2015 18:04:01 (UTC+8)-
dc.date.issued (上傳時間) 10-二月-2015 18:04:01 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/73434-
dc.description.abstract (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.
dc.format.extent 490924 bytes-
dc.format.mimetype application/pdf-
dc.relation (關聯) International Journal of Neuropsychopharmacology, 17(10), 1647-1658
dc.subject (關鍵詞) 5-HT2A receptor;methamphetamine;psychosis
dc.title (題名) Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice
dc.type (資料類型) articleen
dc.identifier.doi (DOI) 10.1017/S1461145714000455en_US
dc.doi.uri (DOI) http://dx.doi.org/10.1017/S1461145714000455en_US