A procedure to identify persistent and effort-independent individual differences in preference for heroin over rewarding social interaction

Background and purpose: In some individuals, opioid use leads to decreased interest in socially relevant rewards. Recent studies showed that after extended-access heroin self-administration, rats strongly prefer social interaction over single unit-dose heroin infusions. We hypothesized that this strong social preference results from access to a suboptimal heroin dose during testing, and individual differences in heroin versus social choice would emerge if rats were given access to their 'preferred' heroin dose. Experimental approach: In Experiment 1, we trained male rats to lever-press for social interaction, followed by heroin self-administration under continuous-access, no-timeout schedule, which promotes burst-patterned heroin taking. We then tested the rats for choice between single-unit heroin dose and 1-min full-contact social interaction, or 5-min heroin-access (sufficient for burst-patterned heroin taking) and 5-min social interaction. In Experiment 2, we extended the 5-min access procedure to female rats and tested heroin versus limited-contact (screen-based) social interaction. We also manipulated response requirements (effort) for heroin. Key results: Rats given a single-unit heroin dose during choice testing, strongly preferred social interaction. In rats given 5-min heroin-access, large individual differences in heroin preference emerged. These differences were independent of sex, social-interaction conditions and effort manipulations. High heroin intake and burst-patterned heroin taking during self-administration, and high heroin seeking during abstinence predicted individual differences in heroin preference. Conclusion and implications: Access to 'preferred' heroin doses during the choice tests leads to stable and effort-independent individual differences in heroin preference. This procedure provides a platform to study mechanisms of resilience and vulnerability to opioid addiction.