Abstract

Cocaine is powerfully rewarding in humans and lower animals. The brain stimulation reward paradigm offers an interesting tool with which to study the reward-relevant actions of cocaine. Cocaine potentiates the rewarding impact of brain stimulation; the stimulation is thought to exert its reward-relevant effects on neural circuitry that subsumes the rewarding effects of cocaine and natural rewards such as food. In the present experiments the curve-shift rate-frequency variant of the brain stimulation reward paradigm was used to characterize the reward-potentiating actions of cocaine in rats lever-pressing for lateral hypothalamic brain stimulation. In Experiment 1 a dose-response curve of cocaine's potentiation of brain stimulation reward was determined and served as a reference for the dosages tested in subsequent experiments. In Experiment 2 repeated intermittent injections of cocaine failed to sensitize cocaine's ability to potentiate brain stimulation reward as would be predicted from the drug self-administration and conditioned place-preference literature. In Experiment 3, the widely held notion that tolerance to the rewarding effects of cocaine contributes significantly to the cocaine habit was tested in the brain stimulation reward paradigm. The reward-potentiating effects of cocaine failed, however, to undergo tolerance with repeated high-dose drug administration. In Experiment 4 a dose of cocaine or amphetamine that causes a 0.3-log unit shift of the rate-frequency curve to the left canceled the effects of a dose of the dopamine antagonist pimozide that causes a 0.3-log unit shift to the right. These findings further suggest that cocaine and amphetamine act as synergists of brain stimulation reward and provide additional evidence of the importance of dopaminergic function in mediating the reward-relevant actions of cocaine and amphetamine. Fischer 344 and Lewis rat strains have been hypothesized to be differentially sensitive to the reward-relevant effects of cocaine. In Experiment 5, however, cocaine produced an equipotent potentiation of brain stimulation reward in the two rat strains. These results suggest that factors other than the reward-relevant effects of cocaine may account for previously reported differences between these two rat strains.