Discrete-trials heroin self-administration produces sensitization to the reinforcing effects of cocaine in rats

Rationale: The prevalence of cocaine use in opioid-dependent individuals is reportedly high, and the associated negative health and social consequences are severe and well documented. Sensitization of the reinforcing effects of cocaine has been demonstrated following noncontingent opioid exposure in animals; however, no preclinical studies have investigated the impact of opioid self-administration on cocaine's reinforcing effects. Objective: Experiments were designed to investigate whether access to heroin self-administration altered the subsequent reinforcing effects of cocaine. Methods: Baseline responding for cocaine under a progressive ratio schedule was first established. Heroin was then self-administered under a 24-h discrete-trials procedure (DT5; access to heroin five times per hour). Subsequently, cocaine-maintained responding was reassessed. Results: Here we demonstrate that 10 days of DT5 heroin self-administration (50 μg/kg per infusion) resulted in an increase in cocaine's reinforcing effects at several doses across the cocaine dose-effect curve (0.38-3.0 mg/kg per infusion). These increases were relatively long lasting, exceeding the time course of a mild withdrawal syndrome. Conclusions: The DT5x10-day history of heroin self-administration resulted in an upward shift in the cocaine dose-effect curve, suggesting that DT5 heroin self-administration produced an increase in potency and sensitization of the maximal effectiveness with which cocaine functions as a reinforcer. The present experiments contribute to a growing amount of preclinical evidence suggesting an impact of opioid exposure on the reinforcing effects of cocaine, which may partially explain the high incidence of cocaine use in opioid-dependent individuals.