GABABeta Regulation of METH-Induced Associative Learning

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DESCRIPTION (provided by applicant): GABAB receptor (GABABR) agonists reduce craving and drug-seeking behaviors; however, they have substantial side effects, which limit their clinical usefulness. GABABR positive allosteric modulators (PAMs) also reduce drug self-administration, but without major motor impairment. PAMs have no direct effect on their own; their utility is directly correlated with the level of GABABR activation by endogenous GABA. Tonic release of GABA is dynamic, and is differentially altered depending upon the dose & duration of drug exposure and the length of drug withdrawal. The following Aims will be used to test the hypothesis that GABABR ligands administered after a sensitizing regimen of methamphetamine (METH) will inhibit the expression of conditioned place preference (CPP) and motor sensitization (MS) and the associated (molecular and functional) changes that occur on the neuronal level. Aim I: To ascertain if GABABR ligands reduce the expression of METH-induced CPP in rats. Aim II: To ascertain if GABAB receptor activation in the medial dorsal thalamus is critical to inhibit the expression of METH-induced CPP. Aim III: Determine if there is a change in GABABR function in rats showing METH-induced CPP and if this is reversed by treatment with GABABR ligands.