title: Brain region specific modulation of ethanol-induced depression of GABAergic neurons in the brain reward system by the nicotine receptor antagonist mecamylamine.
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.
authors: Addiction Biology Unit, Institute of Neuroscience and Physiology, Gothenburg University, Box 410, 40530 Gothenburg, Sweden. Electronic address: louise.adermark@neuro.gu.se.
authors: Louise
authors: L
authors: Adermark
authors: Addiction Biology Unit, Institute of Neuroscience and Physiology, Gothenburg University, Box 410, 40530 Gothenburg, Sweden; Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Bo
authors: B
authors: Söderpalm
authors: Champalimaud Neuroscience Programme, Champalimaud Center for the Unknown, Lisbon, Portugal; Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.
authors: John M
authors: JM
authors: Burkhardt
mesh_terms: D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D018733:Nicotinic Antagonists; D000431:Ethanol; D008464:Mecamylamine
keywords: Alcohol; GABA; Nucleus accumbens; Reward; VTA; nAChR