کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5815767 | 1115527 | 2012 | 10 صفحه PDF | دانلود رایگان |
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.
⺠THIP dose-dependently decreased ethanol intake in two drinking paradigms in C57BL/6J male mice. ⺠Ganaxolone shifted the pattern of drinking and time and dose-dependently altered ethanol intake. ⺠GABAA receptors may regulate ethanol intake at both synaptic and extrasynaptic receptors.
Journal: Neuropharmacology - Volume 63, Issue 4, September 2012, Pages 555-564