DRUGS OF ABUSE AND BRAIN STIMULATION REWARD IN THE MOUSE

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DESCRIPTION (provided by applicant): In recent years a Major thrust in the study of the characteristics of the drug abuser has focused on vulnerability, the possible role that genetics play in this vulnerability, and the molecular underpinnings of the mechanisms of use and relapse into drug use. Intrinsic to the understanding of these problems is the understanding of the mechanisms involved in the action of the abused substances on the brain reward system(s). However, for the most part, researchers have made use of the rat as the animal of choice for study, while most of the experiments on genetic differences make use of mouse as the experimental animal. In trying to investigate the behavior of these genetic mutations investigators have relied mostly on simple unconditioned behavior. The proposed research is designed to adapt for the mouse techniques for measuring the changes in brain-stimulation reward (BSR) that have been successfully used in the rat. The procedures are 1) a discrete trial, rate independent, psychophysical method for measuring the BSR threshold and 2) a parallel procedure that measures the ability of the animal to attend to a stimulus by measuring the detection of non-rewarding stimulation from the same brain site. In addition to measuring the stimulation thresholds, latency of response is also measured. Thus the techniques allow for the determination of not only changes in the reward system but also whether these changes are confounded by motor and attention factors. The proposed experiments will explore differences in response to morphine and cocaine in CB57/B6 and D, and DAT deficient mutant mice. Successful development of these procedures in mice will allow a more specific understanding of the nature of specific phenotypes that may have relationships to the human condition.