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Rationale We have previously reported that cocaine selfadministration is facilitated in male rats not residing in the test chambers (Non Resident rats) relative to rats living in the test chambers at all times (Resident rats). Surprisingly, the opposite was found for heroin. Materials and methods We predicted that, when given access to both cocaine and heroin on alternate days, Non Resident rats would take more cocaine relative to heroin than Resident rats. Heroin (25.0 μg/kg) and cocaine (400 μg/kg), were made alternately available for 14 self-administration sessions, on a fixed ratio (FR) schedule that was progressively increased from FR1 to FR5. Next, some rats underwent a progressiveratio procedure for heroin and cocaine. The other rats continued to alternate heroin and cocaine self-administration for 12 additional sessions, during which the FR schedule was progressively increased from FR10 to FR100. The second aim of the study was to investigate Fos mRNA expression in Resident and Non Resident rats treated with non-contingent intravenous infusion of “self-administration doses” of heroin (25.0 μg/kg) and cocaine (400 μg/kg). Results We found that: (1) drug-taking context differentially modulates intravenous cocaine versus heroin selfadministration; (2) very low doses of cocaine and heroin are sufficient to induce Fos mRNA expression in the posterior caudate; (3) drug-administration context differentially modulates cocaineversus heroin-induced Fos mRNA expression. Conclusions Our study indicates that the context of drug taking can play a powerful role in modulating cocaine versus heroin intake in the laboratory rat.

Drug context differently regulates cocaine versus heroin self-administration and cocaine- versus heroin-induced Fos mRNA expression in the rat