Oxytocin and drug extinction in prairie voles - Project Summary/Abstract Drug abuse is a serious worldwide public health problem [1-3]. While the majority of research has focused on potential neuropharmacological interventions [2], social connection and social affiliation also have profound effects on drug addiction [4, 5]. Not only do positive social connection and social interaction prevent and/or reduce drug use and dependence, they also facilitate drug reward extinction [4]. Unfortunately, studies on the interaction between drug addictive behaviors and the social environment are limited. This is partially due to the difficulties inherent in studying neurobiological mechanisms in humans as well as the fact that traditional laboratory rodent species show limited adult attachment behavior [6-8]. Recently, the socially monogamous prairie vole (Microtus ochrogaster) has emerged as an alternate and unique rodent model for investigating the role of social environment on addictive behaviors. In prairie voles, social bonding between mating partners (pair bonding) [7, 9] and familiar cage mates (peer bonding) [10, 11] can be tested by using the partner preference paradigm. The rewarding value of the psychostimulant amphetamine (AMPH) can be assessed in this species using an established conditioned place preference (CPP) paradigm [12]. Using the combination of those two behavioral paradigms, interactions between social bonding and AMPH reward have been shown and neurochemicals, such as oxytocin (OXT) and dopamine have been implicated in regulating such interactions [13-15]. These findings illustrate the utility of this unique animal model for such investigation [6, 8]. Recently, our data have shown that, in female prairie voles, the presence of a peer partner facilitates AMPH CPP extinction. This social facilitation of AMPH CPP extinction can be impaired by the peer partners’ own AMPH experience but rescued by brain administration of OXT. Here we propose to use the prairie vole model to systematically study the effects of peer partners on facilitating AMPH CPP extinction and the underlying OXT-mediated mechanisms. Specifically, in Aim 1, we propose to establish and validate the behavioral paradigms and to characterize the sex differences in, and the impact of the partner’s drug experience on, the social facilitation of AMPH CPP extinction. In Aims 2 and 3, we will focus on the nucleus accumbens to examine changes in OXT release and OXT receptor (OXTR) expression associated with AMPH CPP extinction, and then examine how pharmacological OXTR manipulation or viral-mediated chemogenetic inhibition/activation of OXT pathway activity alter social facilitation of AMPH CPP extinction. Together, data from this study will not only enhance our understanding of the social facilitation of drug reward extinction and the potential therapeutically relevant mechanisms that underlie it but will also further establish a much-needed animal model to investigate the profound effects of social environment on drug addictive behaviors.
