title: Chronic Intermittent Ethanol Regulates Hippocampal GABA(A) Receptor Delta Subunit Gene Expression.
abstract: Chronic ethanol consumption causes structural and functional reorganization in the hippocampus and induces alterations in the gene expression of gamma-aminobutyric acid type A receptors (GABAARs). Distinct forced intermittent exposure models have been used previously to investigate changes in GABAAR expression, with contrasting results. Here, we used repeated cycles of a Chronic Intermittent Ethanol paradigm to examine the relationship between voluntary, dependence-associated ethanol consumption, and GABAAR gene expression in mouse hippocampus. Adult male C57BL/6J mice were exposed to four 16-h ethanol vapor (or air) cycles in inhalation chambers alternated with limited-access two-bottle choice between ethanol (15%) and water consumption. The mice exposed to ethanol vapor showed significant increases in ethanol consumption compared to their air-matched controls. GABAAR alpha4 and delta subunit gene expression were measured by qRT-PCR at different stages. There were significant changes in GABAAR delta subunit transcript levels at different time points in ethanol-vapor exposed mice, while the alpha4 subunit levels remained unchanged. Correlated concurrent blood ethanol concentrations suggested that GABAAR delta subunit mRNA levels fluctuate depending on ethanol intoxication, dependence, and withdrawal state. Using a vapor-based Chronic Intermittent Ethanol procedure with combined two-bottle choice consumption, we corroborated previous evidences showing that discontinuous ethanol exposure affects GABAAR delta subunit expression but we did not observe changes in alpha4 subunit. These findings indicate that hippocampal GABAAR delta subunit expression changes transiently over the course of a Chronic Intermittent Ethanol paradigm associated with voluntary intake, in response to ethanol-mediated disturbance of GABAergic neurotransmission.
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Floris
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
authors.forename: Gino P
authors.initials: GP
authors.lastname: Asuni
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari Cagliari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ibba
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari Cagliari, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Tocco
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari Cagliari, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Zicca
authors.affiliation: Department of Biomedical Sciences, University of Sassari Sassari, Italy.
authors.forename: Beniamina
authors.initials: B
authors.lastname: Mercante
authors.affiliation: Department of Biomedical Sciences, University of Sassari Sassari, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Deriu
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gorini
keywords: GABA; addiction; alcoholism; dependence; gene expression