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Brain region specific modulation of ethanol-induced depression of GABAergic neurons in the brain reward system by the nicotine receptor antagonist mecamylamine

Journal article
Authors Louise Adermark
Bo Söderpalm
J. M. Burkhardt
Published in Alcohol
Volume 48
Issue 5
Pages 455-461
ISSN 0741-8329
Publication year 2014
Published at Institute of Neuroscience and Physiology
Pages 455-461
Language en
Links dx.doi.org/10.1016/j.alcohol.2014.0...
Keywords Alcohol, GABA, nAChR, Reward, Nucleus accumbens, VTA, VENTRAL TEGMENTAL AREA, ACCUMBAL DOPAMINE OVERFLOW, NUCLEUS-ACCUMBENS, ACETYLCHOLINE-RECEPTORS, REINFORCING PROPERTIES, GLYCINE RECEPTORS, SUBSTANTIA-NIGRA, AVERSIVE STIMULI, C57BL/6J MICE, RAT, Substance Abuse, Pharmacology & Pharmacy, Toxicology, IODO LA, 1984, NEUROSCIENCE, V12, P1, SSA GL, 1985, BRAIN RESEARCH, V348, P201
Subject categories Pharmacology and Toxicology, Substance Abuse

Abstract

The mechanisms underlying ethanol-induced activation of the mesolimbic dopamine system are not fully understood, but increased extracellular dopamine in the nucleus accumbens (nAc) has been shown to involve nicotinic acetylcholine receptors (nAChRs). Basal activity of dopaminergic neurons in the ventral tegmental area (VTA) is under the influence of GABAergic neurotransmission, and the aim of this study was to characterize the involvement of nAChRs in mediating acute ethanol effects on GABAergic activity in subregions of the brain reward system. Multi-electrode in vivo recordings were made in the VTA and nAc of awake and behaving C57BL6/J mice receiving intraperitoneal injections of saline or ethanol (2.0 g/kg), combined with, or without, pre-injection of the non-competitive nAChR antagonist mecamylamine (1.0 mg/kg). Ethanol significantly decreased the activity of quinpirole-insensitive slow-spiking and fast-spiking units in both the VTA and the nAc as compared to saline injection. Pre-treatment with mecamylamine inhibited the rate-inhibiting properties of ethanol in the VTA, but not in the nAc. The data presented here show that ethanol depresses the activity of quinpirole-insensitive, putative GABAergic neurons, in the mesolimbic dopamine system of mice, and that nAChRs contribute to this modulation. This finding, taken together with previous microdialysis studies, supports an involvement of GABAergic neurons and nAChRs in ethanol's interaction with the mesolimbic dopamine system. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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