Targeting Glycine Reuptake in Alcohol Seeking and Relapse.

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.