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Targeting Glycine Reuptake in Alcohol Seeking and Relapse
Valentina Vengeliene1, Martin Roßmanith2, Tatiane T Takahashi2
1Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (V.V., M.R., T.T.T., R.S.); Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland (D.A.); Department of Pharmacology, Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany (B.B., A.B.); and Department of Psychopharmacology, Pavlov Medical University, St. Petersburg, Russia (A.B.) valentina.vengeliene@zi-mannheim.de.
Abstract:
It has recently been demonstrated that pharmacological blockade of the glycine transporter 1 (GlyT1) reduced alcohol intake and relapse in rats. The aim of the present study was to further explore the role of GlyT1 in alcohol relapse-like behavior. For this purpose we used three different GlyT1 blockers-SSR504734, A-1246399, and RO4993850-and tested their effect on alcohol-seeking and relapse-like consumption. Two behavioral models, the alcohol deprivation effect model and the cue-induced reinstatement model, were used. Our data show that all three GlyT1 blockers reduce relapse-like alcohol consumption and cause either minimal or no side effects, measured as changes in home-cage activity, water intake, and body weight. In the reinstatement test, GlyT1 blockers completely abolished alcohol-seeking responses. Furthermore, we tested other drug/cue associations and found that cocaine-seeking responses were also abolished by GlyT1 blockade. Our data confirm that GlyT1 can be used as a target to develop novel anticraving and antirelapse drugs.
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