Preclinical research in addiction is stymied by a translational problem. This impasse is due to limitations in the construct and predictive validity of animal models of addiction, which rarely incorporate social factors. In humans, adverse social interactions and social isolation promote drug self-administration and relapse, while prosocial interactions has a protective role. The cellular and circuit mechanisms underlying the protective effect of volitional social interaction on drug addiction are unknown. To address this gap in knowledge, we have recently developed an operant social-based voluntary abstinence (SVA) procedure and found that rats with a history of social interaction and methamphetamine (Meth) self-administration (SA) strongly prefer social interaction over Meth infusions. SVA also prevented the emergence of Meth craving and our preliminary results suggests that is doing so by preventing the accumulation of Calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). The present proposal is relevant to Sapienza missions (reduce the burden of illnesses), because it explores the neurobiological mechanisms associated to the protective effect of social interaction on Meth craving. Notably, the animal model is homologous to the clinical scenario of the social community reinforcement approach, a behavioral strategy largely employed in the context of drug relapse prevention.
Based on our preliminary data and the literature, in Aim 1 we contrast the forced and SVA animal models of drug craving and investigate similarities and differences in the synaptic adaptations underlying Meth craving occurring in the NAc. Next, in Aim 2 we propose to explore the paraventricular nucleus (PVN) --> NAc projections (and the role of oxytocin) on the protective effect of social-based voluntary abstinence on Meth craving.
