Discriminative stimulus effects of ethanol, pregnanolone, and dehydroepiandrosterone (DHEA) in rats administered ethanol or saline as adolescents

Adolescent alcohol use may produce long-term changes in the receptors and neurosteroids that putatively mediate alcohol's effects and consequently contribute to alcohol abuse and dependence as an adult. To test this possibility, ethanol (0.18-1.8 g/kg) and two neurosteroids, pregnanolone (1-10 mg/kg) and dehydroepiandrosterone (DHEA, 1-100 mg/kg), were administered alone and in combination to adult, male Long-Evans rats discriminating 1 g/kg ethanol (15% v/v) under a fixed ratio (FR) 20 schedule of food presentation after adolescent treatment with 15 injections of ethanol (n = 9, 2 g/kg, 20% v/v) or saline (n = 7). When compared as adults, ethanol-treated adolescents (as opposed to saline-treated adolescents) had higher percentages of ethanol-lever responding at doses smaller than the training dose, and higher response rates after both control and ethanol injections. Neither pregnanolone nor DHEA substituted for ethanol in either adolescent-treated group up to doses that substantially decreased response rates. When administered with ethanol, 1 and 3.2 mg/kg of pregnanolone enhanced the discriminative stimulus effects of small ethanol doses more in saline-treated adolescents than in ethanol-treated adolescents. Unlike pregnanolone, 32 and 100 mg/kg of DHEA attenuated the discriminative stimulus effects of ethanol modestly in both adolescent-treated groups. These results in adult rats suggest that adolescent ethanol administration can enhance the discriminative stimulus effects of small ethanol doses and affect the capacity of pregnanolone, but not DHEA, to interact with ethanol's discriminative stimulus effects.