Drug discrimination analysis of endogenous neuroactive steroids in rats

Nancy A. Ator, Kathleen A. Grant, Robert H. Purdy, Steven M. Paul, Roland R. Griffiths

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.

Original languageEnglish (US)
Pages (from-to)237-243
Number of pages7
JournalEuropean Journal of Pharmacology
Volume241
Issue number2-3
DOIs
StatePublished - Sep 14 1993
Externally publishedYes

Keywords

  • Behaviour
  • Benzodiazepines
  • Drug discrimination
  • Ethanol
  • Neuroactive steroids
  • Pentobarbital

ASJC Scopus subject areas

  • Pharmacology

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