Targeting retrieval of methamphetamine reward memory in the context of REM sleep deprivation: Age-dependent role of GABAB receptors

Abstract

GABA_B receptors play a modulatory role in the mechanisms underlying drug addiction, sleep problems, and aging; however, there are few studies addressing their relationships to each other. Therefore, this study aimed to examine whether blockade of these receptors affects methamphetamine (METH) reward memory in adult and adolescent rapid-eye movement sleep-deprived (RSD) rats. Adolescent and adult male Wistar rats were subjected to RSD for seven days. They were then conditioned to receive methamphetamine (METH; 2 mg/kg, ip) during an eight-day conditioning period. METH reward memory was then reactivated during a retrieval trial and the GABA_B receptor agonist baclofen (2.5 or 5 mg/kg, ip) was injected prior to the retrieval trial. Afterward, animals were retested for the expression of conditioned place preference (CPP) and hippocampal expression of GABA_B receptors. Baclofen dose-dependently decreased the retrieval of METH reward memory in control and RSD adult and adolescent rats, but its effects were stronger at the higher dose. Moreover, we found stronger effects of baclofen in adolescent animals than in adult ones. In addition, baclofen at its higher dose decreased GABA_B overexpression in the hippocampus of adolescent rats, but not in adult rats. These findings shed new light on the mechanisms underlying the role of GABA_B receptors in the retrieval of METH reward memory and highlight the importance of considering age and sleep problems in understanding addiction. Further research could potentially lead to the development of therapeutics for individuals struggling with METH addiction.