Alcoholism is a major public health problem in the United States and many parts of the world. There exists a strong positive association between alcohol consumption and cigarette smoking (nicotine intake). In contrast to nicotine, however, no specific receptor for ethanol has been found. The mesolimbic dopaminergic pathway projecting from the ventral tegmenta area (VTA) to the nucleus accombens (NACC) is believed to be intimately involved in the reinforcing properties of the addictive drugs including alcohol and nicotine. Nicotinic receptors are present in both VTA and NACC. There is strong suggestion that the stimulatory action of ethanol on the mesolimbic system might also be mediated by nicotinic receptors located in this pathway. This proposal will test the hypotheses that 1) activation of nicotinic receptors promotes the actions of ethanol in a brain reward pathway, and 2) alcohol preferring P rats have an altered nicotinic receptor-mediated response to ethanol when compared with stock Wistar and alcohol- nonpreferring NP rats. Micro dialysis and HPLC-EC procedures will be used to determine the dose-response effects of micro injecting nicotinic agonists (nicotine and cytisine) or antagonist (mecamylamine) into the VTA and measuring extracellular levels of DA in the shell portion of the NACC of Wistar rats. Moreover, the effects of a sub- maximal dose of nicotine microinjected into the VTA, on ethanol- induced DA release inthe NACC shell of the Wistar, P, and NP rats will be evaluated. This pilot project will provide essental preliminary data to pursue more extensive studies to examine the involvement of nicotinic receptors in alcoholism and alcohol abuse. This line of research has the potential of leading to novel pharmacotherapies for simultaneous interventions in alcoholism and smoking cessation.
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