ENDORPHINS AND BRAIN REWARD MECHANISMS

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Animals learn to perform behaviors if they are appropriately reinforced when doing so. However, not all rewards lead to behaviors acceptable to a culture, e.g., drug-seeking behavior. It is thus critical to obtain a better understanding of the anatomy and neurochemistry of brain reward mechanisms, both for its heuristic as well as practical value. Numerous experimental models for studying brain reward have been developed, including self-administration, place preference and brain stimulation (ICS). Most have concentrated on a single modality. This project is designed to bridge the gap between brain chemistry and behavior by providing insights into the anatomic and neurochemical mechanisms subserving the expression of behavioral responses to rewarding and aversive environmental stimuli. Endogenous opioid peptides have been implicated as mediators of these stimuli. To this end, in vivo autoradiography of opiate receptors (a measure of receptor occupancy and thus a marker of endorphinergic activity) is being proposed. This will provide a "snapshot' of brain opiate activity during reinforced behaviors and verify the existence of specific chemical/anatomic circuits which engender and maintain reward behavior. Specifically, animals will be trained to respond for ICSm with or without superimposition of an environmental stressor--footshock. The dual properties of opioids in analgesia and reward implies a close relation between brain mechanisms processing these qualities. For an organism to survive in its environment, continuous discriminations must be performed about the relative affective qualities of environmental cues. The aim of this project is to examine the neurochemical and anatomic changes which occur while an animal performs such behaviors. Long-term objectives of this project are to postulate brian mechanisms of the novelty and/or commonality of reward. This may then lead to speculations about the level at which abused drugs impact on this putative reward circuitry, leading perhaps to better understanding and pharmacologic modification or interruption of he reinforcing efficacy of stimulants, opiates, alcohol, etc., which might be directed either at the receptor level (i.e., naltrexone) or by intervening at "reward" sites independent of the drug's direct sites of action.