Alcohol and Alcoholism Advance Access originally published online on November 9, 2006
Alcohol and Alcoholism 2007 42(1):11-18; doi:10.1093/alcalc/agl085
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THE GLYCINE REUPTAKE INHIBITOR ORG 25935 DECREASES ETHANOL INTAKE AND PREFERENCE IN MALE WISTAR RATS
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Sahlgrenska Academy, Göteborg University and Beroendekliniken, Sahlgrenska University Hospital Göteborg, Sweden
*Author to whom correspondence should be addressed at: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Sahlgrenska Academy, Box 410, 405 30 Gothenburg, Sweden; Tel.: +46 31 773 3977; Fax: +46 31 828163; E-mail: bo.soderpalm{at}neuro.gu.se
Received 5 March 2006; first review notified 18 April 2006; first review notified 10 June 2006; accepted 28 August 2006
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Abstract |
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Previous findings from our group indicate that accumbal glycine receptors (GlyRs) are involved in mediating the dopamine (DA) activating effects of ethanol (EtOH), and that administration of glycine locally into the nucleus accumbens (nAc) reduces EtOH consumption in EtOH high-preferring rats. Aims: The present study examines the influence of a systemically administered glycine reuptake inhibitor, Org 25935, on EtOH preference and intake, in male Wistar rats with an EtOH preference >60% (during continuous access to a bottle of EtOH, 6% v/v, and a bottle of water), called EP>60 rats, as well as in animals with an EtOH preference <60%, called EP<60 rats. Org 25935 is an inhibitor of the glycine transporter 1 (GlyT1) protein with negligible action on the glycine transporter 2 (GlyT2) protein. Methods: Both EP>60 and EP<60 rats were limited to drink 2.5 h/day. Org 25935 or vehicle was administered intraperitoneally 
40 min before the rats were presented to a choice of drinking EtOH or water. Results: Org 25935 decreased EtOH intake and EtOH preference, as compared with vehicle, whereas water intake was unaffected. This effect was dose-dependent, developed gradually and was sustained for up to 40 days, also after introduction of an alcohol deprivation period. Conclusion: It is suggested that Org 25935, and possibly also other GlyT1 inhibitors, can represent a new pharmacological treatment principle for alcohol dependence or abuse.
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