Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

摘要

Heightened impulsivity and differential sensitivity to a drug's behavioral effects are traits that, individually, have been associated with chronic drug use and dependence. Here, we used an animal model to test whether individual differences in cocaine-induced activity are predictive of impulsive choice behavior. Adult, male Sprague-Dawley rats were given cocaine (10 mg/kg, i.p.) and classified into low or high cocaine responders (LCRs and HCRs, respectively) based on their locomotor response in an open-field arena. Rats were then trained in a delay-discounting task that offers a choice between immediately delivered, but smaller reinforcements, or larger reinforcements that are delivered after a delay. We also examined the effects of amphetamine (AMPH; 0.3-1.0 mg/kg) and the 5-HT1A agonist 8-OH-DPAT (0.3-1.0 mg/kg) on delay discounting. Lastly, all rats were retested in the open-field to determine if phenotypes were stable. We observed baseline differences in choice behavior between the groups, with HCRs behaving more impulsively (i.e., choosing the small reinforcement) compared to LCRs. AMPH decreased choice of the large reinforcement in LCRs, but did not alter choice in HCRs. Impulsive choice was increased in both phenotypes following 8-OH-DPAT, with LCRs exhibiting changes across a wider range of delays. When cocaine-induced open-field behavior was retested, responses in LCRs were similar whereas HCRs showed evidence of tolerance. Our results suggest that differential sensitivity to cocaine-induced locomotion is predictive of impulsivity and the potential neurobiological differences in LCRs and HCRs may provide insight into mechanisms contributing to vulnerability for chronic drug use and/or dependence.