title: Acamprosate suppresses ethanol-induced place preference in mice with ethanol physical dependence.
abstract: 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.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Matsushima 577, Kurashiki 701-0192, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuno
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Higashioka
authors.forename: Michiko
authors.initials: M
authors.lastname: Oka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hirouchi
authors.forename: Seitaro
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D000077443:Acamprosate; D000280:Administration, Inhalation; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008032:Limbic System / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000427:Alcohol Deterrents; D013654:Taurine; D000431:Ethanol; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D000077443:Acamprosate