A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Behav Pharmacol. 2012 Jun;23(3):250-61. doi: 10.1097/FBP.0b013e32835342d2.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / drug therapy*
  • Animals
  • Dehydroepiandrosterone / analogs & derivatives*
  • Dehydroepiandrosterone / pharmacology*
  • Ethanol / blood*
  • Male
  • Rats
  • Rats, Long-Evans
  • Reinforcement, Psychology
  • Yohimbine / pharmacology

Substances

  • 7-oxodehydroepiandrosterone
  • Yohimbine
  • Ethanol
  • Dehydroepiandrosterone