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Ethanol‐Induced Regulation of GABA A Subunit mRNAs in Prefrontal Fields of Cynomolgus Monkeys
Author(s) -
Hemby Scott E.,
O'Connor Joann A.,
Acosta Glen,
Floyd Donald,
Anderson Nancy,
McCool Brian A.,
Friedman David,
Grant Kathleen A.
Publication year - 2006
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2006.00254.x
Subject(s) - protein subunit , prefrontal cortex , neuroscience , ethanol , chemistry , biology , psychology , microbiology and biotechnology , biochemistry , gene , cognition
Background: Recent evidence indicates that functional impairment of the orbital and medial fields of the prefrontal cortex may underlie the deficits in executive control of behavior that characterize addictive disorders, including alcohol addiction. Moreover, previous studies have indicated that alcohol alters GABA neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting the GABA A receptor complex. Given that GABAergic transmission has an integral role in cortical processing, influencing local and interregional communication, understanding alcohol‐induced alterations in GABA A receptors in prefrontal fields of the primate brain may provide insight into the functional impairment of these brain regions in the alcohol‐addicted state and extend our understanding of the molecular consequences of long‐term use in these critical brain regions. Methods and Results: To address this problem, the effects of chronic ethanol self‐administration in male cynomolgus monkeys on GABA A receptor subunit mRNA expression was studied in 3 frontal cortical fields: orbitofrontal cortex (OFC; area 13), anterior cingulate cortex (ACC; area 24), and the dorsolateral prefrontal cortex (DLPFC; area 46). Quantitative polymerase chain reaction revealed significant alterations in GABA A subunit mRNA expression in the OFC and DLPFC but not in the ACC. Specifically, expression of the α 2, α 4, β 1, β 3, and γ 1 to γ 3 subunit mRNAs was significantly less in the OFC, whereas the expression of β 1, β 2, γ 1, and δ subunit mRNAs was less in the DLPFC of alcohol‐treated monkeys. Conclusion: These findings suggest that ethanol‐induced alterations in GABA A function may be due to alterations in GABA A subunit mRNA levels and subunit‐specific alterations are selective to particular cortical fields.