Administration of GABAB receptor positive allosteric modulators inhibit the expression of previously established methamphetamine-induced conditioned place preference

Little is known about the role of GABAB receptors (GABABRs) in the maintenance of memories associated with using abused substances. We have embarked on a series of studies designed to determine if enhancing the efficacy of GABA-occupied GABABRs with positive allosteric modulators (PAMs) can negate previously established conditioned place preference (CPP) induced by methamphetamine. In the current study, we evaluated the effects of acute administration of GABABR PAMs, GS39783 and CGP7930. We determined that post-conditioning treatments with these PAMs, administered in the home cage, blocked the subsequent expression of methamphetamine-induced CPP. These data indicate that selectively augmenting GABA-occupied GABABR signaling is sufficient to reduce memory maintenance and/or the salience of contextual cues previously associated with methamphetamine.

Research highlights▶ Methamphetamine place preference is disrupted by GABAB receptor modulators. ▶ Memory maintenance is disrupted by augmenting endogenous GABA. ▶ GABAB receptor positive allosteric modulators may treat psychostimulant addiction.