An investigation of endogenous neuroactive steroid-induced modulation of ethanol's discriminative stimulus effects

Behav Pharmacol. 1999 May;10(3):297-311. doi: 10.1097/00008877-199905000-00006.


Neuroactive steroids exhibit rapid non-genomic central nervous system activity, including modulation of GABAA and NMDA receptors, two receptors known to mediate the effects of methanol. Neuroactive steroids that modulate GABAA receptors in a manner similar to ethanol were expected to potentiate the discriminative stimulus and/or rate-suppressing effects of ethanol. In contrast, neuroactive steroids that modulate GABAA or NMDA receptors in a manner opposite to ethanol were hypothesized to attenuate the effects of ethanol. Adult male rats were trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) from water (i.g.). Animals were pretreated with subthreshold doses (i.p.) of ethanol and neuroactive steroids and exposed to an acute stressor (n = 5), prior to conducting ethanol cumulative-dosing (i.p.) tests. Only ethanol and 3 beta, 5 beta-P pretreatments potentiated the discriminative stimulus effects of ethanol. None of the six neuroactive steroid manipulations attenuated the effects of ethanol. These results demonstrate that a neuroactive steroid, endogenous in humans, can enhance the interoceptive effects of ethanol.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Alcohol Drinking / psychology
  • Animals
  • Brain / drug effects
  • Discrimination Learning / drug effects*
  • Discrimination Learning / physiology
  • Dose-Response Relationship, Drug
  • Male
  • Pregnanolone / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / physiology


  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Pregnanolone