Positive allosteric modulation of the GABA(B) receptor by GS39783 attenuates the locomotor stimulant actions of ethanol and potentiates the induction of locomotor sensitization.

Alcohol
Lauren C KruseStephen L Boehm

Abstract

Acute ethanol-induced locomotor stimulation and ethanol-induced locomotor sensitization are two behavioral assays thought to model the rewarding effects of ethanol. Recent evidence suggests that GS39783, a GABA(B) positive allosteric modulator, may be effective at reducing both the rewarding and reinforcing effects of several drugs of abuse, including ethanol. The goal of this study was to determine if GS39783 was capable of altering acute ethanol-induced stimulation, and the induction and expression of ethanol-induced locomotor sensitization, without effecting basal locomotion levels. Several doses of GS39783 (ranging from 0 to 100 mg/kg, depending on experiment) were tested on adult male DBA/2J mice in four experiments using 3-day basal locomotion and acute ethanol stimulation paradigms, and 14-day induction and expression of ethanol sensitization paradigms. The results of experiment 1 are in agreement with current literature, suggesting that 30 mg/kg doses of GS39783 and lower do not alter basal locomotor activity. In experiment 2, we found that GS39783 significantly decreased acute ethanol stimulation, but only at the 30 mg/kg dose, supporting our hypothesis and other publications suggesting that GABA(B) receptors modulate ...Continue Reading

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Citations

Jun 8, 2013·Addiction Biology·David N Linsenbardt, Stephen L Boehm
Apr 21, 2016·Brain Research Bulletin·Rosana Camarini, Ricardo Marcos Pautassi
Mar 27, 2013·The Journal of Pharmacology and Experimental Therapeutics·L C HullW L Dewey

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