Ethanol-like discriminative stimulus effects of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in female Macaca fascicularis monkeys

Kathleen A. Grant, Alexey Azarov, Carrie A. Bowen, Serene Mirkis, Robert H. Purdy

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The present study was designed to characterize the discriminative stimulus effects of ethanol and the neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) in non-human primates. Female cynomolgus monkeys (Macaca fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg ethanol (IC, 30 min pretreatment) from water using food reinforcement. Consistent with previous results in a variety of species, pentobarbital (0.56-17 mg/kg, IG) resulted in a dose-dependent substitution for the discriminative stimulus effects of ethanol, with an average ED50 value of 1.9 mg/kg. Administration of allopregnanolone (0.3-5.6 mg/kg, IV) also produced complete substitution for the discriminative stimulus effects of ethanol, with an ED50 value of 1.0 mg/kg. Plasma allopregnanolone levels 35 min following the administration of 3.0 mg/kg allopregnanolone ranged from 33 to 69 ng/ml. The ethanol-like discriminative stimulus effects of 1.0 mg/kg allopregnanolone (IV) were present for 60 min, with a return to complete water-appropriate responding at 90 min post-treatment. The results indicate that the endogenous neuroactive steroid allopregnanolone produces subjective effects in cynomolgus monkeys that are similar to ethanol. These findings suggest that changes in the endogenous levels of allopregnanolone could alter sensitivity to the subjective effects of ethanol.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalPsychopharmacology
Volume124
Issue number4
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • 3α-hydroxy-5α-pregnan-20-one
  • drug discrimination
  • ethanol
  • monkeys
  • neuroactive steroids
  • neurosteroids
  • pentobarbital

ASJC Scopus subject areas

  • Pharmacology

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