title: A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule.
abstract: Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectivity for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol-maintained and food-maintained responding, compared with the control, while also decreasing the blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared with food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, whereas it did not affect ethanol-maintained responding compared with the control. Low to intermediate doses of rauwolscine produced small, nonsignificant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence.
authors.affiliation: Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, USA. Russell.j.amato@vanderbilt.edu
authors.forename: Russell Joseph
authors.initials: RJ
authors.lastname: Amato
authors.forename: Mary Worrel
authors.initials: MW
authors.lastname: Hulin
authors.forename: Peter John
authors.initials: PJ
authors.lastname: Winsauer
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C002914:7-oxodehydroepiandrosterone; D015016:Yohimbine; D000431:Ethanol; D003687:Dehydroepiandrosterone