The proposed research is based on the working hypothesis that psychomotor stimulants and opiates derive their abuse liability from actions in diencephalic motivational mechanisms which have been partially characterized on the basis of brain stimulation studies. Five lines of study are aimed at increasing our understanding of these systems and their interactions with these classes of drugs of abuse. The first examines the relationship between diencephalic reward mechanisms (already implicated in opiate and psychomotor stimulant effects) and hindbrain reward mechanisms. The boundaries of selected hindbrain reward sites will be precisely defined, and the connectivity between hindbrain and diencephalic reward sites will be determined. The second examines the relation of the mechanisms of reward to the mechanisms of drive-like stimulation effects. Are the circuits of brain stimulation reward the same or independent of the drive-like effects of stimulation at the same brain sites? The third examines the effects of drugs of abuse and their blockers on stimulation-induced drive-like and rewarding effects. Do these drugs influence stimulation-induced eating, drinking, and locomotion at the same sites and doses as influence stimulation-induced reward? Do the same doses of the same drugs at the same sites influence both the drive-like and the rewarding effects of stimulation? The fourth examines the effects of these drugs on natural motivational effects. Do the drugs facilitate deprivation-induced eating and drinking and lever-pressing for food and water when administered at the same central sites and doses as are effective with brain stimulation reward and stimulation-induced eating and drinking? The fifth explores the question of whether opiates and psychomotor stimulants are rewarding in their own right when administered at the sites and doses where they influence these stimulation-induced and natural motivational functions. Are the site of action and the relative potencies of various opioids and stimulants in reward paradigms predicted from their effects in brain stimulation paradigms? These studies are intended to increase our knowledge of the basic neurobiology of motivational mechanisms and of the effects of drugs of abuse in such mechanisms.
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