The finding that DHEA, a neurosteroid and prohormone available over the counter for a variety of conditions, decreases voluntary consumption of alcohol in rats trained to consume ethanol (14) is an exciting one. However, the mechanism by which DHEA decreases alcohol intake is not clear, nor has the effectiveness of DHEA been compared to more traditional treatments for alcoholism. The proposed study will address these issues in the following ways: 1) To determine whether the decrease of ethanol intake mediated by DHEA is comparable to decreases induced by drugs traditionally used to treat alcohol abuse (i.e., naltrexone and acamprosate), the effects of DHEA on ethanol intake will be compared to naltrexone and acamprosate using a voluntary drinking procedure in rats;2) DHEA will be administered to rats trained in an ethanol drug discrimination procedure to test the hypothesis that DHEA decreases ethanol intake by decreasing the discriminative effects of ethanol;and 3) To show DHEA can affect the subunit composition and subunit expression of GABAA receptors, which will help illustrate the integral relationship among DHEA, the GABAA receptor complex, and ethanol intake, immunohistochemistry experiments will be performed on rat brains following a period of chronic DHEA administration. Together, these aims will provide significant data regarding the potential of a known substance, DHEA, to serve as a pharmacotherapy for alcohol abuse and dependence, and provide important data on the potential mechanism of action of DHEA's effects on alcohol intake.
About 8 million individuals in the United States currently meet the criteria for alcohol dependence (3), costing Americans approximately $185 billion annually (16). Despite the prevalence and costliness of this problem, there are only five approved pharmacotherapies for alcohol dependence in the US and Europe (41). This study will investigate the clinical utility of DHEA as a treatment for alcohol abuse, which, along with tobacco and illicit drug use, is responsible for 1 in 4 deaths in the United States (16).
|Hulin, Mary W; Lawrence, Michelle N; Amato, Russell J et al. (2015) Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats. Alcohol 49:127-38|
|Hulin, Mary W; Amato, Russell J; Winsauer, Peter J (2012) GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats. Alcohol Clin Exp Res 36:223-33|
|Amato, Russell Joseph; Hulin, Mary Worrel; Winsauer, Peter John (2012) A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule. Behav Pharmacol 23:250-61|
|Hulin, Mary W; Amato, Russell J; Porter, Johnny R et al. (2011) Neurosteroid Binding Sites on the GABA(A) Receptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence. Adv Pharmacol Sci 2011:926361|