Project Summary Over the last decade, opioid addiction has become increasingly problematic. Clinical research on drug vs. nondrug (e.g., monetary vouchers) choice has demonstrated that nondrug alternative rewards can reduce, or even prevent drug use. Mirroring clinical results, preclinical choice models in rats and nonhuman primates have shown that nondrug food rewards can decrease heroin choice. However, a limitation of animal models of choice has been the exclusive use of food as the nondrug alternative reward. In humans, the alternative rewards that compete with drugs are primarily social rewards (e.g., family, employment). To address this preclinical-clinical research gap, the Shaham lab recently introduced a rat model of operant social self-administration and choice between rewarding social interaction vs. methamphetamine or heroin. The main behavioral finding was that when rats were trained for drug self-administration under different gold- standard addiction models and given mutually exclusive choices between lever pressing for drug or social interaction, they strongly preferred social interaction. The Shaham lab also used the social choice model to study incubation of drug craving, the time-dependent increase in drug seeking after cessation of drug self- administration. In this setup, relapse to drug seeking was assessed after 2 weeks of ‘voluntary abstinence’, achieved by providing rats daily choices between heroin, cocaine, or methamphetamine vs. social interaction. They reported dissociable effects of social choice-induced abstinence on incubation of methamphetamine or cocaine craving (complete blockade) vs. heroin craving (modest decrease) compared with homecage forced abstinence. The neurobiological mechanisms of incubation of heroin craving after social-induced abstinence and the preference for social interaction over opioid drugs are currently unknown. Therefore, the aim of this proposal is to identify the brain areas and circuits underlying (1) incubation of heroin craving after social-induced abstinence and (2) choice between social interaction vs. opioid drugs. The proposal will provide new insights on brain mechanisms underlying relapse to opioid seeking and choice between opioid drugs vs. social interaction using behavioral procedures that more closely mimic the human condition.