Individual differences in elevated plus-maze exploration predicted progressive-ratio cocaine self-administration break points in Wistar rats

There are considerable individual differences in vulnerability to drug addiction, but the mechanisms underlying such differences are poorly understood. Cocaine has potent reinforcing effects that support operant responding. However, cocaine also elicits aversive reactions and produces an approach-avoidance conflict in rats. We hypothesized that preexisting individual differences in open arm exploration on the elevated plus-maze, a well-known model for the study of clinically effective anxiolytic drugs, would predict individual differences in cocaine-motivated behavior. To assess whether individual differences in sensitivity to anxiety-like behavior on the plus-maze predict motivation to self-administer intravenous (i.v.) cocaine. Rats were assessed drug-free for individual differences in open arm exploration on the elevated plus-maze, and later trained to perform an operant response for i.v. cocaine (0, 0.1, 0.3, 0.6, 0.9, 1.2, and 1.5 mg kg(-1) infusion(-1)) on a progressive-ratio reinforcement schedule. Rats were split at the median into low and high open arm explorers based on time spent in the open arms of the plus-maze. Self-administration levels were compared across groups. Rats identified as high open arm explorers on the elevated plus-maze attained higher levels of operant responding for cocaine. Open arm times and break points were significantly correlated at the highest cocaine doses (1.2 and 1.5 mg kg(-1) infusion(-1)). These results indicate that individual differences in anxiety-like behavior on the elevated plus-maze predict motivation to self-administer cocaine, and suggest the possibility that reduced sensitivity to aversive stimuli may be associated with increased vulnerability to the rewarding properties of cocaine.