Tolerance to ethanol is a complex phenomenon, with different types of tolerance resulting from different paradigms of administration of the drug. In order to study tolerance to ethanol in the cardiovascular system, two methods of chronic ethanol administration will be employed. A Pavolvian conditioning model will be used to produce environment-dependent tolerance and a liquid diet technique will be used to produce environment- independent tolerance. With the environment-dependent tolerance paradigm, various cardiovascular parameters will be assessed to determine whether or not the tolerance observed follows the conditioning pattern that has previously been observed for thermal responses. Since changes in ethanol disposition have been noted with this procedure, one aim of this proposal is to assess the possibility that the changes in ethanol disposition could be due to alterations in blood flow. The same cardiovascular parameters will be measured in environment-independent tolerant rats so that a comparison can be made. Dose response curves will be generated in each paradigm for both the amount of ethanol exposure used to generate tolerance and the amount of ethanol used to test tolerance. Thus, progressive changes and any biphasic effects of ethanol can be evaluated. Since hypertension is a common problem in alcoholics, the information obtained in these studies may shed light on the development of mechanisms of this problem.
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