The aim of the proposed study is to characterize changes in opiate receptor function which result from exposure of animals to ethanol. Such changes may be related to the development of tolerance to certain, dopaminergically-mediated, CNS actions of ethanol. The effects of acute and chronic ethanol treatment on morphine and enkephalin modulation of dopamine turnover in striatum, hypothalamus and the mesolimbic area of mouse brain will be evaluated using a sensitive HPLC method. Concomitantly, binding parameters for 3H-dihydromorphine and 3H-2-D-Ala Met-enkephalinamide will be determined in these dopaminergically-innervated brain areas of ethanol-treated and control animals. Possible mechanisms underlying changes in opiate receptor function will be investigated, and the relationship of such changes to ethanol tolerance and/or physical dependence will be assessed. The proposed work will help to elucidate the nature of the CNS adaptive response to ethanol, including the role of cell membrane perturbations in this response. In addition, these investigations will provide specific information on possible interactions between ethanol and the endogenous opioid systems in particular brain areas, and with regard to particular CNS functions.