Acamprosate Suppresses Ethanol-Induced Place Preference in Mice With Ethanol Physical Dependence

• Published in: Journal of Pharmacological Sciences Vol. 122; no. 4; pp. 289 - 298
• Main Authors: Kurokawa, Kazuhiro, Mizuno, Koji, Shibasaki, Masahiro, Higashioka, Masaya, Oka, Michiko, Hirouchi, Masaaki, Ohkuma, Seitaro
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2013; The Japanese Pharmacological Society; Elsevier
• Subjects: Acamprosate; Administration, Inhalation; alcohol dependence; Alcohol Deterrents - pharmacology; Alcoholism - drug therapy; Alcoholism - genetics; Alcoholism - psychology; Animals; conditioned place preference; Conditioning (Psychology) - drug effects; CREB-Binding Protein - metabolism; CREB-Binding Protein - physiology; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic AMP-Dependent Protein Kinases - physiology; Depression, Chemical; Dose-Response Relationship, Drug; ethanol; Ethanol - administration & dosage; Injections, Intraperitoneal; Limbic System - metabolism; Male; Mice; Mice, Inbred Strains; Molecular Targeted Therapy; phospho-cAMP response element binding protein (p-CREB); Signal Transduction - drug effects; Signal Transduction - physiology; Taurine - administration & dosage; Taurine - analogs & derivatives; Taurine - pharmacology; Taurine - therapeutic use; alcohol dependence; conditioned place preference; ethanol; acamprosate; phospho-cAMP response element binding protein (p-CREB)
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.13056FP

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.