The role of environmental context in the vulnerability to relapse into heroin and cocaine addiction: a pre-clinical investigation

Background: We have recently observed an unforeseen dissociation in the effect of environmental context on cocaine versus heroin self-administration (SA) in rats. Rats that were transferred to the SA chambers only for the test sessions (Non Residents) took more cocaine than rats housed in the SA chambers (Residents). The contrary was found for heroin. The aim of the present study was to investigate the influence of context on the ability of different doses of cocaine and heroin priming to reinstate cocaine- vs. heroin-seeking in rats that had been trained to self-administer both drugs and had then extinguished lever pressing behavior. Methods: Resident (N=65) and Non-Resident (N=64) rats with double-lumen intra-jugular catheters were trained to self-administer cocaine (400 μg/kg/infusion) and heroin (25 μg/kg/infusion) on alternate days for 10 consecutive days (3 hours/session/day). After extinction of lever pressing behavior, independent groups of rats were given a non-contingent intra-venous (i.v.) infusion of heroin (25, 50, or 100 μg/kg) or cocaine (400, 800, or 1600 μg/kg) and drug seeking was quantified by counting non-reinforced lever presses. Results: All Resident and Non-Resident rats acquired heroin and cocaine SA and extinguished lever pressing behavior for both drugs. When given cocaine primings only Non Resident rats exhibited reinstatement of cocaine-seeking and, in contrast, when given heroin primings only Resident rats exhibited reinstatement of heroin-seeking. Conclusions: We report that the susceptibility to relapse into drug seeking behavior is drug- and setting-specific, confirming the crucial role played by drug, set, and setting interactions in drug addiction