Acamprosate Suppresses Ethanol-Induced Place Preference in Mice With Ethanol Physical Dependence
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概要
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The present study investigated the effect of acamprosate on ethanol (EtOH)-induced place preference in mice with EtOH physical dependence. The expression of EtOH (2 g/kg, intraperitoneally)-induced place preference in mice without EtOH treatment before the experiment was dose-dependently suppressed by acamprosate. The levels of protein kinase A (PKA) and phospho-cAMP response element binding protein (p-CREB) in the limbic forebrain after EtOH-conditioning in naïve mice was unchanged. Furthermore, mice on the 4th day of withdrawal from continuous EtOH vapor inhalation for 9 days showed transient and significant enhancement of EtOH (1 g/kg, intraperitoneally)-induced place preference, which was significantly suppressed by acamprosate (300 mg/kg, oral administration; p.o., once a day) administered daily for 3 days after withdrawal from EtOH inhalation and during EtOH-conditioning. PKA and p-CREB proteins in the limbic forebrain of EtOH-conditioned mice on 4th day of withdrawal from continuous EtOH inhalation for 9 days significantly increased, which were completely abolished by acamprosate. These findings suggest that the signal transduction pathway via the PKA–p-CREB pathway in the limbic forebrain may be functionally related to the development of sensitization of EtOH-induced place preference and provide a possible molecular basis for the pharmacological effect of acamprosate to prevent or reduce the relapse of alcohol dependence.
著者
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Ohkuma Seitaro
Department Of Pharmacology Kawasaki Medical School
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Mizuno Koji
Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences
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Higashioka Masaya
Research Laboratories Nippon Shinyaku Co. Ltd.
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Oka Michiko
Research Laboratories Nippon Shinyaku Co. Ltd.
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Kurokawa Kazuhiro
Department Of Pharmacology Kawasaki Medical School
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Shibasaki Masahiro
Department Of Pharmacology Kawasaki Medical School
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Mizuno Koji
Department of Pharmacology, Kawasaki Medical School, Japan
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Shibasaki Masahiro
Department of Pharmacology, Kawasaki Medical School, Japan
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Hirouchi Masaaki
Research Laboratories, Nippon Shinyaku Co., Ltd., Japan
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Higashioka Masaya
Research Laboratories, Nippon Shinyaku Co., Ltd., Japan
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