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

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.

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.

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.

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.