Pharmacokinetic insights into behavioral differences in heroin and
cocaine self-administration and choice procedures
Abstract
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.