Behavioural and pharmacokinetic analysis of heroin and cocaine self-administration: Effects of timeout on self-administration and choice in male rats

Abstract

Background and purpose: Heroin and cocaine users tailor their dosage, frequency and administration route to maximise the drugs' effects or prevent withdrawal symptoms. Counterintuitively, preclinical self-administration and choice experiments employ, almost invariably and regardless of the pharmacokinetic properties of the drug under examination, fixed unit-doses and timeouts (after unit-doses) largely resulting in uniform drug-taking patterns. This uniformity contrasts with the large variability observed in humans, which serves as critical indicator of addiction severity and treatment success. Here, by combining behavioural and pharmacokinetics assessments, we revealed that drug self-administration procedures without timeouts may overcome this limitation.

Experimental approach: We analysed heroin- and cocaine-taking patterns and seeking and estimated drug-brain levels in the presence or absence of timeout under different training conditions.

Key results: Removing timeouts had a profound effect on heroin-taking patterns and seeking, promoting the emergence of burst-like intake, yielding higher brain peak concentrations of heroin. In contrast, the removal of timeout had marginal impact on cocaine-taking patterns and seeking.

Conclusion and implications: The removal of timeout during self-administration revealed distinct cocaine and heroin patterns, with the latter closely resembling human heroin use patterns.

Keywords: addiction; animal models; opioids; pharmacokinetics; psychostimulants; self‐administration.