Allopregnanolone and Pentobarbital Infused Into the Nucleus Accumbens Substitute for the Discriminative Stimulus Effects of Ethanol

Hodge, Clyde W. and Nannini, Michelle A. and Olive, M. Foster and Kelley, Stephen P. and Mehmert, Kirstin K. (2001) Allopregnanolone and Pentobarbital Infused Into the Nucleus Accumbens Substitute for the Discriminative Stimulus Effects of Ethanol. Alcoholism: Clinical and Experimental Research, 25 (10). pp. 1441-1447. ISSN 0145-6008. (Full text available)

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Abstract

BACKGROUND: The discriminative stimulus effects of ethanol are mediated in part by the gamma-aminobutyric acid type A (GABA(A)) receptor system. We have previously shown that microinjections of the competitive GABA(A) agonist muscimol in the nucleus accumbens and amygdala fully substitute for the discriminative stimulus effects of systemic ethanol. However, it is not known whether allosteric binding sites on GABA(A) receptors located within specific limbic brain regions contribute to the discriminative stimulus effects of ethanol. METHODS: Male Long-Evans rats were trained to discriminate between intraperitoneal injections of ethanol (1 g/kg) and saline under a fixed-ratio 10 schedule of sucrose (10% w/v) reinforcement. Injector guide cannulae, aimed at both the nucleus accumbens core and the hippocampus area CA1, were then implanted to allow site-specific infusion of GABA(A)-positive modulators. RESULTS: Infusion of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, or 3alpha-5alpha-P) in the nucleus accumbens resulted in dose-dependent full substitution for intraperitoneal ethanol (50% effective dose = 0.38 ng/microl per side). Likewise, injection of the barbiturate pentobarbital into the nucleus accumbens also substituted dose-dependently for ethanol (50% effective dose = 1.55 microg/microl per side). However, infusions of either 3alpha-5alpha-P or pentobarbital in the hippocampus failed to substitute for ethanol and produced inverted U-shaped dose-response curves. CONCLUSIONS: These results demonstrate that allosteric positive modulation of GABA(A) receptors in the nucleus accumbens produces full substitution for the stimulus effects of ethanol. This suggests that GABA(A) receptors in the nucleus accumbens may play a more influential role in the discriminative stimulus effects of ethanol than those in the hippocampus.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Stephen Kelley
Date Deposited: 29 Jun 2011 17:07
Last Modified: 16 Apr 2014 10:26
Resource URI: http://kar.kent.ac.uk/id/eprint/11712 (The current URI for this page, for reference purposes)
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