Possible Interaction: Ethanol and Dehydroepiandrosterone

“ Alcohol also increased pregnenolone (PREG) and dehydroepiandrosterone ( DHEA ) concentrations, while it decreased progesterone (PROG) and allopregnanolone (ALLO) concentrations, as well as ALLO/PREG and PROG/PREG ratios.”

“Unlike pregnanolone, 32 and 100 mg/kg of DHEA attenuated the discriminative stimulus effects of ethanol modestly in both adolescent-treated groups.”

“Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains.”

“Finally, under the multiple schedule, noncontingent injections of ethanol (0.32-1.8 g/kg), DHEA (10-100 mg/kg), and pregnanolone (1.8-32 mg/kg) dose-dependently decreased food- and ethanol-maintained responding and the dose of ethanol presented.”

“Further, we have shown that two neurosteroids, dehydroepiandrosterone (DHEA) and pregnanolone, can readily decrease ethanol self-administration in males.”

“Administration of dehydroepiandrosterone (DHEA), a neurosteroid that can negatively modulate the GABA A receptor, has been shown to decrease voluntary intake of ethanol in rats.”

“Although 10mg/kg of 7-keto DHEA produced decreases similar to those found with DHEA, the 56-mg/kg dose of 7-keto DHEA was significantly more effective at decreasing the dose of ethanol consumed than the same dose of DHEA.”

“Both 10 and 56 mg/kg of 7-keto DHEA significantly reduced the dose of ethanol consumed.”

“In contrast, multiple doses of DHEA consistently decreased intake of an 18% … concentration in both groups after repeated injections and 3 doses of DHEA (10, 32, and 56 …/kg) administered with various ethanol concentrations dose-dependently shifted the ethanol-concentration curves … the volume and dosage of ethanol consumed downward.”

“Ethanol or DHEAS individually had no effect on the AMPA receptor-mediated synaptic component, but application of ethanol after DHEAS resulted in a small enhancement of this synaptic component, an effect that was not observed if ethanol was applied before DHEAS.”

“Such an interaction may be involved in ethanol's actions on the CNS and raises the possibility that ethanol and DHEAS may act via a common site or pathway.”

“These results show that ethanol and DHEAS interact, altering DHEAS's effects on synaptic transmission and LTP in the hippocampus.”

“Both RO15-1788 and PTZ blocked the anxiolytic effect of DHEA, there was no interaction with diazepam, and ethanol enhanced the anxiolytic effect of DHEA.”

“ DHEA enhances the hypothermic effect of both ethanol and pentobarbital.”

“ DHEA , but not DHEAS, causes a dose-dependent increase in the sleep time induced by either ethanol or pentobarbital.”

“ Ethanol gave a marked increase of all 3 beta-hydroxy-delta 5 steroids analyzed: pregnenolone (60%), 17-hydroxypregnenolone (480%), dehydroepiandrosterone (430%) and 5-androstene-3 beta, 17 beta-diol (60%).”