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題名 N-acetylcysteine modulates hallucinogenic 5-HT2A receptor agonist-mediated responses: Behavior, molecular, and electrophysiological studies.
作者 Lee, Mei-Yi ; Chiang, Chun-Cheng ; Chiu, Hong-Yi ; Chan, Ming-Huan ; Chen, Hwei-Hsien
詹銘煥
貢獻者 神科所
關鍵詞 N-acetylcysteine; 5-HT2A receptor; Head twitch; mGluR2 receptor
日期 2014.02
上傳時間 13-六月-2014 16:55:30 (UTC+8)
摘要 N-acetylcysteine (NAC) has been reported to reverse the psychotomimetic effects in the rodent phencyclidine model of psychosis and shown beneficial effects in treating patients with schizophrenia. The effect of NAC has been associated with facilitating the activity of cystine-glutamate antiporters on glial cells concomitant with the release of non-vesicular glutamate, which mainly stimulates the presynaptic metabotropic glutamate receptor subtype 2 receptors (mGluR2). Recent evidence demonstrated that functional interactions between serotonin 5-HT2A receptor (5-HT2AR) and mGluR2 are responsible to unique cellular responses when targeted by hallucinogenic drugs. The present study determined the effects of NAC on hallucinogenic 5-HT2AR agonist (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-elicited behavioral and molecular responses in mice and DOI-evoked field potentials in the mouse cortical slices. NAC significantly attenuated DOI-induced head twitch response and expression of c-Fos and Egr-2 in the infralimbic and motor cortex and suppressed the increase in the frequency of excitatory field potentials elicited by DOI in the medial prefrontal cortex. In addition, the cystine-glutamate antiporter inhibitor (S)-4-carboxyphenylglycine (CPG) and the mGluR2 antagonist LY341495 reversed the suppressing effects of NAC on DOI-induced head twitch and molecular responses and increased frequency of excitatory field potentials, supporting that NAC attenuates the 5-HT2AR-mediated hallucinogenic effects via increased activity of cystine-glutamate antiporter followed by activation of mGluR2 receptors. These findings implicate NAC as a potential therapeutic agent for hallucinations and psychosis associated with hallucinogen use and schizophrenia.
關聯 Neuropharmacology, 15(81), 215-223
資料類型 article
dc.contributor 神科所en_US
dc.creator (作者) Lee, Mei-Yi ; Chiang, Chun-Cheng ; Chiu, Hong-Yi ; Chan, Ming-Huan ; Chen, Hwei-Hsienen_US
dc.creator (作者) 詹銘煥-
dc.date (日期) 2014.02en_US
dc.date.accessioned 13-六月-2014 16:55:30 (UTC+8)-
dc.date.available 13-六月-2014 16:55:30 (UTC+8)-
dc.date.issued (上傳時間) 13-六月-2014 16:55:30 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/66701-
dc.description.abstract (摘要) N-acetylcysteine (NAC) has been reported to reverse the psychotomimetic effects in the rodent phencyclidine model of psychosis and shown beneficial effects in treating patients with schizophrenia. The effect of NAC has been associated with facilitating the activity of cystine-glutamate antiporters on glial cells concomitant with the release of non-vesicular glutamate, which mainly stimulates the presynaptic metabotropic glutamate receptor subtype 2 receptors (mGluR2). Recent evidence demonstrated that functional interactions between serotonin 5-HT2A receptor (5-HT2AR) and mGluR2 are responsible to unique cellular responses when targeted by hallucinogenic drugs. The present study determined the effects of NAC on hallucinogenic 5-HT2AR agonist (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-elicited behavioral and molecular responses in mice and DOI-evoked field potentials in the mouse cortical slices. NAC significantly attenuated DOI-induced head twitch response and expression of c-Fos and Egr-2 in the infralimbic and motor cortex and suppressed the increase in the frequency of excitatory field potentials elicited by DOI in the medial prefrontal cortex. In addition, the cystine-glutamate antiporter inhibitor (S)-4-carboxyphenylglycine (CPG) and the mGluR2 antagonist LY341495 reversed the suppressing effects of NAC on DOI-induced head twitch and molecular responses and increased frequency of excitatory field potentials, supporting that NAC attenuates the 5-HT2AR-mediated hallucinogenic effects via increased activity of cystine-glutamate antiporter followed by activation of mGluR2 receptors. These findings implicate NAC as a potential therapeutic agent for hallucinations and psychosis associated with hallucinogen use and schizophrenia.en_US
dc.format.extent 2486442 bytes-
dc.format.mimetype application/pdf-
dc.language.iso en_US-
dc.relation (關聯) Neuropharmacology, 15(81), 215-223en_US
dc.subject (關鍵詞) N-acetylcysteine; 5-HT2A receptor; Head twitch; mGluR2 receptoren_US
dc.title (題名) N-acetylcysteine modulates hallucinogenic 5-HT2A receptor agonist-mediated responses: Behavior, molecular, and electrophysiological studies.en_US
dc.type (資料類型) articleen