Alphaxalone and epiallopregnanolone in rats trained to discriminate ethanol

Brett C. Ginsburg, R. J. Lamb

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Neurosteroids with a 3α-hydroxy orientation share pharmacological effects with ethanol, increase in brain after ethanol administration, and may mediate ethanol effects. 3β-hydroxy neurosteroids antagonize in vitro and some, but not all in vivo effects of ethanol and 3α-hydroxy neurosteroids. Methods: We assessed the discriminative stimulus and rate altering effects of alphaxalone, a 3α-hydroxy neurosteroid, and epiallopregnanolone, a 3β-hydroxy neurosteroid, in rats trained to discriminate either 0.8 g/kg or 1.2 g/kg ethanol. The ability of epiallopregnanolone to antagonize the discriminative stimulus or rate-altering effects of ethanol or alphaxalone was also assessed. Results: Ethanol had similar discriminative ED50s (0.5 g/kg) in both groups; however rats trained with the lower ethanol dose were more sensitive to rate-decreasing effects of ethanol. Alphaxalone occasioned ethanol-appropriate responding in both training groups, although less effectively in rats trained on the lower ethanol dose (maximum 65% versus 80% ethanol-appropriate responding). No difference in sensitivity to the rate-decreasing effects of alphaxalone was present between groups. Epiallopregnanolone did not reliably occasion ethanol-appropriate responding in either training group, and rats trained on the lower ethanol dose were slightly more sensitive to epiallopregnanolone rate decreasing effects. Epiallopregnanolone did not alter any effects of ethanol or alphaxalone. Conclusions: Our results agree with previous reports that 3α-hydroxy neurosteroids occasion ethanol-appropriate responding, while 3β-hydroxy neurosteroids do not; as well as reports showing no antagonism of the discriminative stimulus or rate-suppressant effects of ethanol or 3α-hydroxy neurosteroids by 3/3-hydroxy neurosteroids. Results of the present study demonstrate that ethanol and 3α-hydroxy neurosteroids share discriminative stimulus effects. However, these results are inconsistent with the hypothesis that such neurosteroids mediate the discriminative stimulus of ethanol.

Original languageEnglish (US)
Pages (from-to)1621-1629
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume29
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • 5α-Pregnanolone
  • Alcohol
  • Drug Discrimination
  • Isopregnanolone
  • Neurosteroid

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Alphaxalone and epiallopregnanolone in rats trained to discriminate ethanol'. Together they form a unique fingerprint.

  • Cite this