BRAIN STIMULATION MODELS OF DRUG ABUSE

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This is a request for a Research Scientist Award (RSA K05). My future research will have as its major commitment the study of abused substances as well as provide a laboratory for training of pharmacology, psychology and behavioral neuroscience graduate and postdoctoral students. The proposed research is directed toward furthering our understanding of the neuronal bases of the rewarding effects of abused substances with special emphasis on the psychomotor stimulants and the abused opioids. Because of previous findings suggesting that the olfactory tubercle may play a role in the rewarding effects of these two classes of abused substances we will focus some of our research on the elucidation of this brain site in the mechanism of drug reward. Also included will be complementary experiments of the analgesic effects of opiate drugs and the manner that non- pharmacological variables may contribute to their analgesic effects. Because of our finding that morphine-induced oral stereotypy in the rat can be re-expressed by a comparatively low dose of morphine months after the initial morphine treatment we have embarked on a series of experiments to determine the mechanisms involved in these long term effects. These experiments may have relevance for both opioid abuse as well as a possible role of the endogenous opioid system in hyperkinetic movement disorders. The procedures used in the study of the rewarding effects of abused substances involve the parenteral as well as intracerebral administration of receptor specific agonist and antagonist. The major methods we use to study the effects of these pharmacological manipulations are brain- stimulation reward, drug self-administration and the quantitative 2-[14C) deoxyglucose method of determining local cerebral glucose utilization.