Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration

Marcia J. Ramaker, Moriah N. Strong, Matthew M. Ford, Deborah A. Finn

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Recent evidence suggests that GABAA receptor ligands may regulate ethanol intake via effects at both synaptic and extrasynaptic receptors. For example, the endogenous neurosteroid, allopregnanolone (ALLO) has a similar pharmacological profile as ethanol, and it alters ethanol intake in rodent models. Additionally, recent evidence suggests that δ-subunit- containing extrasynaptic GABAA receptors may confer high sensitivity to both ethanol and neurosteroids. The purpose of the present study was to determine the effects of ganaxolone (GAN; an ALLO analog) and gaboxadol (THIP; a GABAA receptor agonist with selectivity for the extrasynaptic δ-subunit) on ethanol intake, drinking patterns, and bout characteristics in operant and limited-access self-administration procedures. In separate studies, the effects of GAN (0-10 mg/kg) and THIP (2-16 mg/kg) were tested in C57BL/6J male mice provided with 2-h access to a two-bottle choice of water or 10% ethanol or trained to respond for 30 min of access to 10% ethanol. GAN had no overall significant effect on operant ethanol self-administration, but tended to decrease the latency to consume the first bout. In the limited-access procedure, GAN dose-dependently decreased ethanol intake. THIP dose-dependently decreased ethanol intake in both paradigms, altering both the consummatory and appetitive processes of operant self-administration as well as shifting the drinking patterns in both procedures. These results add to literature suggesting time-dependent effects of neurosteroids to promote the onset, and to subsequently decrease, ethanol drinking behavior, and they support a role for extrasynaptic GABAA receptor activation in ethanol reinforcement.

Original languageEnglish (US)
Pages (from-to)555-564
Number of pages10
JournalNeuropharmacology
Volume63
Issue number4
DOIs
StatePublished - Sep 1 2012

    Fingerprint

Keywords

  • Alcohol
  • Extrasynaptic
  • GABA receptors
  • Lickometer
  • Neurosteroid

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this