Ethanol-induced regulation of GABAA subunit mRNAs in prefrontal fields of cynomolgus monkeys

Abstract

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 GABAA receptor complex. Given that GABAergic transmission has an integral role in cortical processing, influencing local and interregional communication, understanding alcohol-induced alterations in GABAA 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 GABAA 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 GABAA subunit mRNA expression in the OFC and DLPFC but not in the ACC. Specifically, expression of the α2, α4, β1, β3, and γ1 to γ3 subunit mRNAs was significantly less in the OFC, whereas the expression of β1, β2, γ1, and δ subunit mRNAs was less in the DLPFC of alcohol-treated monkeys. Conclusion: These findings suggest that ethanol-induced alterations in GABAA function may be due to alterations in GABAA subunit mRNA levels and subunit-specific alterations are selective to particular cortical fields. Copyright © 2006 by the Research Society on Alcoholism.