
You have already added 0 works in your ORCID record related to the merged Research product.
You have already added 0 works in your ORCID record related to the merged Research product.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://beta.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=undefined&type=result"></script>');
-->
</script>
Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration

Recent evidence suggests that GABA(A) 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 GABA(A) 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 GABA(A) 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 GABA(A) receptor activation in ethanol reinforcement.
- Oregon Health & Science University United States
- United States Department of the Interior United States
- United States Department of the Interior United States
- Oregon Health & Science University United States
Male, Time Factors, Alcohol Drinking, Self Administration, Pregnanolone, Mice, Animals, GABA-A Receptor Agonists, Molecular Targeted Therapy, Nootropic Agents, Dose-Response Relationship, Drug, Ethanol, Drugs, Investigational, Isoxazoles, Receptors, GABA-A, Mice, Inbred C57BL, Protein Subunits, Conditioning, Operant, Reinforcement, Psychology, Alcohol Deterrents
Male, Time Factors, Alcohol Drinking, Self Administration, Pregnanolone, Mice, Animals, GABA-A Receptor Agonists, Molecular Targeted Therapy, Nootropic Agents, Dose-Response Relationship, Drug, Ethanol, Drugs, Investigational, Isoxazoles, Receptors, GABA-A, Mice, Inbred C57BL, Protein Subunits, Conditioning, Operant, Reinforcement, Psychology, Alcohol Deterrents
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).25 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
