Ethanol markedly increases "GABAergic'' neurosteroids in alcohol-preferring rats

Alcohol administration (1 g/kg, i.p.) increased the levels of the neuroster oids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, THD OC) in the cerebral cortex and hippocampus both in alcohol-naive Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats (two rat lines selec tively bred for alcohol preference and non-preference, respectively). Howev er, the increase reached several fold higher levels in sP than in sNP rats (6-24 vs. 2-11 fold the basal levels, respectively). Since the two neuroste roids are the most potent endogenous positive modulators of GABA(A) recepto rs and elicit anxiolytic and rewarding effects, while voluntary alcohol con sumption produces anxiolytic and rewarding effects in sP but not in sNP rat s, the results suggest that the neurosteroids may play a role in the anxiol ytic and rewarding effects of alcohol in sP rats. (C) 1999 Elsevier Science B.V. All rights reserved.