Cocaine self-administration in rats with histories of cocaine exposure and discrimination

Rationale: Interrelationships between the discriminative stimulus and reinforcing properties of psychoactive drugs and the way in which they may interact to control drug intake are unclear. Studies have shown that drug history can influence the expression of drug-produced behavioral effects. Objective: The present study examined the acquisition and maintenance of intravenous cocaine self-administration in rats with a history of drug discrimination. Methods: Two groups of male hooded rats (n = 12 each) were successfully trained in a single-lever food-reinforced procedure to discriminate cocaine (10 mg/kg) from saline. Control groups (n = 12 each) received drug injections and/or saline injections only and lever-pressed for food reinforcers with no discrimination training. Subsequently, all subjects were implanted with chronic jugular catheters and allowed to nose-poke for infusions of cocaine (0.2 mg/kg per infusion). Results: Initial rates of responding were similar for all groups. Acquisition of self-administration on a FR-10 schedule of drug delivery was significantly faster for cocaine-exposed rats in comparison to all other groups (P < 0.02). There were no differences between groups in the breaking points of cocaine and saline on a progressive ratio schedule of self-administration. Dose-response functions were obtained by two methods and were similar for all groups. Conclusion: These results are consistent with earlier studies demonstrating weakly sensitized primary reinforcing properties of cocaine in preexposed rats. Previous learning to discriminate cocaine impaired this sensitization.