Translating human drug use patterns into rat models: exploring spontaneous interindividual differences via refined drug self-administration procedures
Users of heroin and cocaine self-regulate the dosage and frequency of administration to experience drugs' rewarding effects and avoid withdrawal. In contrast, most preclinical self-administration and choice procedures use experimenter-imposed unit-doses and timeout after infusions. Here, we introduce a no-timeout procedure that overcomes this limitation. We analyzed the heroin and cocaine taking- and seeking-patterns and estimated drug-brain levels in the presence or absence of timeout between drug injections. We further assessed the effect of timeout and drug or social peer access time on drug preference. Removing the timeout had a profound effect on pattern of heroin taking and seeking, promoting the emergence of burst-like drug intake. Timeout removal had a modest effect on cocaine taking and seeking. Drug or social peer access time increased heroin but not cocaine preference. Removal of timeout during self-administration and increasing the access time during choice resulted in a self-administration procedure that more closely mimic human heroin intake, offering a platform to identify novel medications.