GABAA RECEPTOR MODULATION DURING ADOLESCENCE ALTERS ADULT ETHANOL INTAKE AND PREFERENCE IN RATS.
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
To test the hypothesis that GABAA modulation during adolescence can increase the probability of alcohol abuse during adulthood, the effects of adolescent administration of both positive and negative GABAA modulators were assessed on adult alcohol preference. Three groups of adolescent male rats received 15 injections on alternate days from postnatal day (PD) 35 to 65. One group received the benzodiazepine and positive GABAA modulator lorazepam, another received the neurosteroid and negative GABAA modulator DHEA, and the last received vehicle. Doses of 3.2 mg/kg of lorazepam and 56 mg/kg of DHEA were administered for the initial twelve injections, whereas 5.6 mg/kg and 100 mg/kg, respectively, were administered for the last three injections. During this period, the acute effects of these doses on food intake were also measured under two levels of food access, either 25-30 g/day or 18-20 g/day. On both injection and non-injection days, food presentation occurred at the same time of day and food intake was measured after 60 min; all drug injections occurred just prior to food presentation. Ethanol intake and preference was assessed when subjects reached adulthood (PD 90) by giving each group 24-hr concurrent access to three bottles containing water, saccharin, or an ethanol/saccharin solution (0.05% saccharin with 5, 10, or 18% ethanol). The ratio of ethanol to saccharin was increased incrementally every three days over a twelve-day period, and the intake of each solution was recorded daily. In adolescence, food intake in lorazepam-treated subjects was increased during the 60-minute test on injection days compared to non-injection days and compared to DHEA-and vehicle-treated subjects. This effect was enhanced by the more restrictive feeding schedule. Food intake in DH EA-treated subjects was decreased compared to non-injection days, but not compared to vehicle-treated subjects. In adulthood, the preference for each solution differed among treatment groups and across ethanol concentrations. Lorazepamtreated subjects preferred the two lowest concentrations of ethanol/saccharin over saccharin alone, whereas both vehicle-treated and DHEA-treated subjects showed no preference for any concentration of ethanol/saccharin over saccharin. These data demonstrate that GABAA modulation during adolescence alters intake and preference for ethanol in adulthood, and highlights the importance of drug history in the liability for alcohol abuse.
Recommended Citation
Worrel, Mary Beth; Amato, R. J.; and Winsauer, P. J., "GABAA RECEPTOR MODULATION DURING ADOLESCENCE ALTERS ADULT ETHANOL INTAKE AND PREFERENCE IN RATS." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 24.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/24
GABAA RECEPTOR MODULATION DURING ADOLESCENCE ALTERS ADULT ETHANOL INTAKE AND PREFERENCE IN RATS.
To test the hypothesis that GABAA modulation during adolescence can increase the probability of alcohol abuse during adulthood, the effects of adolescent administration of both positive and negative GABAA modulators were assessed on adult alcohol preference. Three groups of adolescent male rats received 15 injections on alternate days from postnatal day (PD) 35 to 65. One group received the benzodiazepine and positive GABAA modulator lorazepam, another received the neurosteroid and negative GABAA modulator DHEA, and the last received vehicle. Doses of 3.2 mg/kg of lorazepam and 56 mg/kg of DHEA were administered for the initial twelve injections, whereas 5.6 mg/kg and 100 mg/kg, respectively, were administered for the last three injections. During this period, the acute effects of these doses on food intake were also measured under two levels of food access, either 25-30 g/day or 18-20 g/day. On both injection and non-injection days, food presentation occurred at the same time of day and food intake was measured after 60 min; all drug injections occurred just prior to food presentation. Ethanol intake and preference was assessed when subjects reached adulthood (PD 90) by giving each group 24-hr concurrent access to three bottles containing water, saccharin, or an ethanol/saccharin solution (0.05% saccharin with 5, 10, or 18% ethanol). The ratio of ethanol to saccharin was increased incrementally every three days over a twelve-day period, and the intake of each solution was recorded daily. In adolescence, food intake in lorazepam-treated subjects was increased during the 60-minute test on injection days compared to non-injection days and compared to DHEA-and vehicle-treated subjects. This effect was enhanced by the more restrictive feeding schedule. Food intake in DH EA-treated subjects was decreased compared to non-injection days, but not compared to vehicle-treated subjects. In adulthood, the preference for each solution differed among treatment groups and across ethanol concentrations. Lorazepamtreated subjects preferred the two lowest concentrations of ethanol/saccharin over saccharin alone, whereas both vehicle-treated and DHEA-treated subjects showed no preference for any concentration of ethanol/saccharin over saccharin. These data demonstrate that GABAA modulation during adolescence alters intake and preference for ethanol in adulthood, and highlights the importance of drug history in the liability for alcohol abuse.