Background: In some individuals, opioid use leads to a 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. Methods: 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 (or binge-like) heroin intake. We then tested the rats for choice between single-unit heroin dose and 1-minute full-contact social interaction, or 5-minute heroin-access (sufficient for binge-like intake) and 5-minute social interaction. In Experiment 2, we extended the 5-minute access procedure to female rats and tested heroin versus limited-contact (screen-based) social interaction. We also manipulated response requirements (effort) for heroin. Results: When rats were given a single-unit heroin dose during choice testing, they strongly preferred social interaction. In contrast, when given 5-minute 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 binge-like intake during self-administration, and high heroin seeking during abstinence predicted individual differences in heroin preference. Conclusions: 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.

Background and Purpose. Heroin and cocaine users tailor their dosage, frequency, and method of administration, to maximize the drugs’ effects or prevent withdrawal symptoms. Counterintuitively, preclinical self-administration and choice experiments employ fixed unit-doses and timeouts (after doses) largely resulting in uniform drug-taking patterns. The application of these procedures also disregards the distinct pharmacokinetic properties of heroin and cocaine. This uniformity contrasts with the significantly different ways humans tailor their dosage and frequency of heroin and cocaine use. Here, by combining behavioral and pharmacokinetics assessments we revealed that self-administration procedures lacking the timeout may overcomes this limitation. Experimental Approach. We analyzed heroin and cocaine taking- and seeking-patterns and estimated drug-brain levels in the presence or absence of timeout. We further assessed how absence of timeout and the availability of drug or social peer (access time to the two rewards) affect drug preference in choice procedures. Key Results. Removing the timeout had a profound effect on heroin-taking patterns and seeking, promoting the emergence of burst-like intake, yielding higher brain peak concentrations of heroin. Timeout removal had marginal impact on cocaine taking patterns and seeking. Increasing the access time to the drug in the discrete choice procedure resulted in higher drug intake and increased preference for heroin, but it did not alter cocaine preference. Conclusion and Implications. Removing timeout during self-administration revealed distinct heroin and cocaine taking patterns. Self-administration without timeout and access to high heroin doses during choice more closely mimic human heroin taking patterns and related behaviors, including maladaptive choices.