Effect of social choice-induced voluntary abstinence on incubation of methamphetamine craving and AMPA receptor expression in nucleus accumbens core

Pre-clinical studies on drug addiction and relapse often overlooked volitional social interactions, which are of critical importance in human addiction. Recently, it has been demonstrated that social choice-based voluntary abstinence in rats attenuates the emergence of incubation of methamphetamine (Meth) craving relative to rats subjected to a forced abstinence. In the current study we investigated the molecular mechanisms by which social choice-based voluntary abstinence prevents the incubation of craving. An important mechanism driving cue-induced craving from psychostimulants in forced abstinent rats, is the accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the Nucleus Accumbens core. This accumulation strengthens glutamatergic transmission in medium-spiny neurons (MSNs) hence intensifying drug-seeking responses. In the current study we investigated whether social choice-based voluntary abstinence prevents CP-AMPAR accumulation in the Nucleus Accumbens core, thereby reducing the incubation of craving. We indeed observed that social choice-based voluntary abstinence significantly reduces the incubation of Meth craving, however this effect was independent of the CP-AMPAR accumulation in the Nucleus Accumbens. Alternative plasticity mechanisms likely occur in parallel in the NAc during social interaction, which lead to a reduced drug-seeking in social voluntary rats.