The proposed research consists of a series of experiments designed to continue our current efforts to explore the neurobehavioral bases for the rewarding effects of ethanol. We will attempt to determine the effects of ethanol on the sensitivity to rewarding electrical brain stimulation in rats which have undergone manipulation of various neurotransmitter systems. Dopamine has been implicated in the reinforcing effects of a variety of commonly abused substances (e.g., opiates, cocaine). If ethanol also affects reward in a similar way, an up-regulated dopamine system might result in enhanced rewarding effects of ethanol in the brain stimulation reward (BSR) paradigm. Ethanol induced sedation which can initially confound reward assessment has been attributed in part to GABA mediation. Experiments involving the direct interaction of ethanol with indirect GABA agonists (e.g. benzodiazepines) on BSR and the manipulation of GABA systems by chronic administration of such agonists are proposed. It has also been suggested that ethanol may exert rewarding effects via an endogenous opiate system. Since we have found increased sensitivity to the rewarding effects of BSR after repeated exposures to morphine, it may then be possible to induce a similar increase by chronic ethanol administration. If an increased sensitivity to ethanol also coexists with one to morphine on BSR, it would suggest a similar mechanism may be operating for both agents. Associative factors may influence how ethanol affects an organism. These may include methods of administration, contingent or noncontingent administration, and taste. To control for taste and its influence on contingent versus noncontingent administration we will determine the effects on BSR in rats self-administering ethanol via a gastric cannula. In the final group of studies the effects of opiates and psychomotor stimulants on the sensitivity for BSR in ethanol preferring (P) and nonpreferring (NP) lines of rats will be determined. Because the difference in ethanol preference between these two strains may be due to a difference in sensitivity to the rewarding effects, we will determine if animals differ in the rewarding effects of other abused drugs, as assessed by BSR. Taken together these experiments should provide us with further insight into the reinforcing properties of ethanol, and more firmly establish neurochemical bases for its rewarding nature.
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