Neuroactive Steroid Stereospecificity of Ethanol-Like Discriminative Stimulus Effects in Monkeys□S

Positive modulation of GABAA and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (pro-gesterone) [allopregnanolone (3,5-P), pregnanolone (3,5-P), epiallopregnanolone (3,5-P), and epipregnanolone (3,5-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3,5-P HS)], and a structurally similar, adrenally derived steroid [3-hydroxy-5-androstan-17-one (3,5-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administra-tion in male (n 9) and female (n 8) cynomolgus monkey