DEHYDROEPIANDROSTERONE SELECTIVELY DECREASES RESPONDING FOR ETHANOL UNDER A MULTIPLE SCHEDULE OF FOOD AND ETHANOL REINFORCEMENT IN RATS.
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
Our laboratory has shown that dehydroepiandrosterone (DHEA) dose-dependently decreases voluntary alcohol intake in rats. However, the mechanism and selectivity of this effect is unknown. The purpose of this study was to determine whether the observed decrease in alcohol intake is selective for ethanol or if DHEA affects behavior maintained by other reinforcers similarly, as well as to determine if the effects of DHEA are due to its metabolism to sex steroids. To assess this, male Long-Evans rats trained to respond under a multiple schedule of food and ethanol presentation were administered doses of ethanol (0.32 -1.8 g/kg), DHEA (1 O -180 mg/kg) or 7-keto DH EA ( 1 Oand 56 mg/kg) prior to the session. 7-keto DH EA is a metabolite of DHEA that is not metabolized to sex steroids. In one component of the multiple schedule, responding (lever press) was reinforced under a fixed-ratio (FR)-1 Oschedule of ethanol presentation (0.1 ml of 32% v/v), whereas responding in the other component was reinforced under a FR-20 schedule of food presentation (45mg food pellet). Components of ethanolreinforced responding (1 Ominutes) alternated with components of food-reinforced responding (5 minutes) for 60 minutes. Dependent measures of responding under this schedule were response rate (response/minute), volume of ethanol presented (ml), and blood alcohol concentration (BAC; mg/di). Ethanol injected prior to the session selectively decreased both the rate of responding for ethanol and the volume of ethanol presented in six of seven subjects. Although somewhat less selectively, DHEA and 7-keto DHEA also decreased response rate and the volume of ethanol presented in the ethanol component. Unlike ethanol, which did not decrease BACs, both DHEA and 7-keto DHEA dose-dependently decreased BACs. Responding during the food-reinforced component was not altered substantially except at the highest doses of all three drugs. Together, these results demonstrate that DHEA and 7-keto DHEA can produce relatively selective effects on ethanol-maintained behavior as well as dose-dependently decrease BACs in rats. Because 7keto DHEA decreased responding for ethanol more potently than DHEA, these data also demonstrate that DHEA's conversion to the sex steroids is not necessary to produce decreases in ethanol-reinforced responding.
Recommended Citation
Amato, Russel and Worrel, M. E., "DEHYDROEPIANDROSTERONE SELECTIVELY DECREASES RESPONDING FOR ETHANOL UNDER A MULTIPLE SCHEDULE OF FOOD AND ETHANOL REINFORCEMENT IN RATS." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 2.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/2
DEHYDROEPIANDROSTERONE SELECTIVELY DECREASES RESPONDING FOR ETHANOL UNDER A MULTIPLE SCHEDULE OF FOOD AND ETHANOL REINFORCEMENT IN RATS.
Our laboratory has shown that dehydroepiandrosterone (DHEA) dose-dependently decreases voluntary alcohol intake in rats. However, the mechanism and selectivity of this effect is unknown. The purpose of this study was to determine whether the observed decrease in alcohol intake is selective for ethanol or if DHEA affects behavior maintained by other reinforcers similarly, as well as to determine if the effects of DHEA are due to its metabolism to sex steroids. To assess this, male Long-Evans rats trained to respond under a multiple schedule of food and ethanol presentation were administered doses of ethanol (0.32 -1.8 g/kg), DHEA (1 O -180 mg/kg) or 7-keto DH EA ( 1 Oand 56 mg/kg) prior to the session. 7-keto DH EA is a metabolite of DHEA that is not metabolized to sex steroids. In one component of the multiple schedule, responding (lever press) was reinforced under a fixed-ratio (FR)-1 Oschedule of ethanol presentation (0.1 ml of 32% v/v), whereas responding in the other component was reinforced under a FR-20 schedule of food presentation (45mg food pellet). Components of ethanolreinforced responding (1 Ominutes) alternated with components of food-reinforced responding (5 minutes) for 60 minutes. Dependent measures of responding under this schedule were response rate (response/minute), volume of ethanol presented (ml), and blood alcohol concentration (BAC; mg/di). Ethanol injected prior to the session selectively decreased both the rate of responding for ethanol and the volume of ethanol presented in six of seven subjects. Although somewhat less selectively, DHEA and 7-keto DHEA also decreased response rate and the volume of ethanol presented in the ethanol component. Unlike ethanol, which did not decrease BACs, both DHEA and 7-keto DHEA dose-dependently decreased BACs. Responding during the food-reinforced component was not altered substantially except at the highest doses of all three drugs. Together, these results demonstrate that DHEA and 7-keto DHEA can produce relatively selective effects on ethanol-maintained behavior as well as dose-dependently decrease BACs in rats. Because 7keto DHEA decreased responding for ethanol more potently than DHEA, these data also demonstrate that DHEA's conversion to the sex steroids is not necessary to produce decreases in ethanol-reinforced responding.