This research is directed toward furthering our understanding of the neuronal bases of the reinforcing effects of abused substances with special emphasis on the opiates and the psychomotor stimulants, e.g. cocaine. Included will be complementary studies of the analgesic effects of opiate drugs and the manner that non-opioid systems may contribute to these effects. The major neurobehavioral model that we use for the study of the reinforcing effects of abuse substances is brain-stimulation reward. We have consistently found that all drugs that lower the threshold for rewarding electrical stimulation to the brain, are abused, have potential for abuse as confirmed by independent criteria. or in a few cases have effects on non-reward systems that would preclude use. Using the brain-stimulation reward model we plan a series of experiments to determine the extent that identical neuronal systems are involved in the mediation of the threshold lowering effects of the opiate drugs and the psychomotor stimulants. The 2-(14C)deoxyglucose method of determining local cerebral glucose utilization (LCGU). use of the neurotoxin 6-OHDA, and the interaction of the effects of dopamine and opiate antagonists with drugs that lower the threshold for rewarding brain simulation will be studied. In order to determine if there are differences in neuronal systems involved in the reinforcing and the analgesic effects of opiates. morphine's effects on LCGU will be compared in animals working to receive rewarding brain stimulation, or to escape from nociceptive brain stimulation.
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