The proposed research is based on the view that drugs of abuse have their rewarding impact (and thus their abuse liability) because of their ability to pharmacologically activate brain circuitry involved in natural reward function and natural ingestive behaviors.
The aim of the proposed studies is to advance the understanding of drug abuse by advancing the understanding of brain reward mechanisms and how drugs interact with them. Brain reward systems will be studied using electrophysiological and neuropharmacological techniques, with particular interest in the involvement of dopaminergic and opioid peptides in reward function. The 14 specific aims for the next funding period are: to map the anatomy of brain stimulation reward (BSR) more extensively; to assess more fully the effects of radical dopaminergic destruction on BSR; to further develop paradigms for discriminating drug effects on motor function from those on reward function; to rank-order various neuroleptics relative to their attenuation of BSR; to dissociate task demands from reward effectiveness as a factor in neuroleptic challenge of lever-pressing behavior; to assess the effect of rewarding brain stimulation and reward-associated central morphine injections on striatal and limbic dopamine release; to further quantify the effects of opiates on BSR; to explore the effects of ethanol, barbiturates and benzodiazepines on BSR using new and more sensitive paradigms; to determine the effects of intracranial opiate receptor blockade on BSR; to determine the effects of opiate receptor blockade on reward facilitation by ethanol, barbiturates and benzodiazepines (should these drugs prove to reliably facilitate BSR); to determine the effects of neuroleptics on food reward as reflected in a free-feeding task; to determine the effects of intracranial neuroleptics on food reward; to determine the effect of intracranial morphine on food reward and feeding behavior; to map the substrate for turning behavior elicited by central morphine injections. It is hoped that these studies will advance the understanding of the anatomical circuitry at which drugs of abuse have their interface with the mechanisms of behavioral control by the brain.
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