The impact of discrete versus continuous dimensions strategies in heroin and cocaine self-administration on drug-taking patterns and social interaction.

Background: During their drug-use history, cocaine and heroin users gain mastery and control over their drug consumption. Indeed, they self-regulate the dosage, route, speed, and frequency of administration as a function of the expected effects (e.g., avoid withdrawal, experiencing euphoria, etc.). Counterintuitively, most preclinical self-administration and choice procedures use discrete dimension strategies, featured by experimenter-imposed unit-doses interspersed by timeouts, which prevent the experimental animal to self-select the appropriate dose-time relationship of administration. Here, we contrasted discrete to continuous dimension strategies (i.e., self-selected doses without timeout) that allow to do so. Methods*: We analyzed the drug-taking patterns and modeled drug-brain levels (PK profiling) under distinct self-administration training conditions, featured by the presence or absence of time-out between consecutive drug injections. We further assessed the motivation to take and seek drugs across training conditions and in the context of drug-vs-social choice procedures. Results: The drug-taking patterns, and related PK profiling, were profoundly different across both training conditions and drug under examination. Continuous dimension strategy resulted in an increased heroin intake and promoted the emergency of drug-taking patterns characterized by the injection of spaced and large doses of drug, resulting in high and fast-rising brain levels of heroin. By contrast, cocaine intake was only slightly increased and there were no differences in the drug-taking patterns. Notably, we did not observe overdoses in rats trained without a timeout, contrary to what the literature would have anticipated. Rather, the lack of timeout was associated with stronger motivation to take and seek drugs. Finally, by employing a continuous dimension strategy we described, for the first time, social withdrawal after heroin, but not cocaine self-administration in rats. Conclusions: Here, we provide evidence advocating for the implementation of continuous, rather than discrete dimension strategies in self-administration and choice procedures because more accurately mirror human-drug-related behaviors (and likely the neural adaptations).