Ethanol-induced regulation of GABA-A subunit mRNAs in prefrontal fields of cynomolgus monkeys.

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.

Distinct functional characteristics of the lateral/basolateral amygdala GABAergic system in C57BL/6J and DBA/2J mice.

It is generally understood that genetic mechanisms contribute to pathological anxiety and that C57BL/6 (B6) and DBA/2J (D2) mice, inbred strains differing markedly in their anxiety-like behaviors, may represent a model system to study these contributions. Because lateral/basolateral amygdala (BLA) GABA(A) receptors help regulate anxiety-like behaviors, we have tested the hypothesis that differences in receptor function/expression may be related to strain-specific differences in experimentally measured anxiety. First, we demonstrated that anxiety-like behaviors in two separate assays were more substantial in D2 mice.

Chronic ethanol ingestion modulates proanxiety factors expressed in rat central amygdala.

Withdrawal anxiety following chronic ethanol exposure is often associated with relapse in recovering alcoholics. It is likely that brain regions regulating anxiety-like behaviors adapt during chronic ethanol exposure to ultimately regulate such behaviors. The central amygdala contains numerous neurotransmitter systems that have been implicated in the regulation of anxiety-like behavior, including corticotropin releasing factor (CRF) and NMDA-type glutamate receptors.

Long-term ethanol self-administration by cynomolgus macaques alters the pharmacology and expression of GABAA receptors in basolateral amygdala.

We have recently demonstrated that chronic ethanol ingestion alters the functional and pharmacological properties of GABAA receptors measured in acutely isolated rat lateral/basolateral amygdala neurons, a limbic forebrain region involved with fear-learning and innate anxiety. To understand relevance of these results in the context of primates, we have examined the effects of long-term ethanol self-administration on basolateral amygdala GABAA receptor pharmacology and expression in cynomolgus macaques (Macaca fascicularis). The impact of this 18-month-long exposure on GABAA receptor function was assessed in acutely isolated neurons from basolateral amygdala with whole-cell patch-clamp electrophysiology.

Chronic ethanol ingestion facilitates N-methyl-D-aspartate receptor function and expression in rat lateral/basolateral amygdala neurons.

Withdrawal anxiety after chronic alcohol is likely to contribute to drug seeking and relapse in alcoholics. The brain regions regulating fear/anxiety behaviors, especially neurotransmitter systems with acute ethanol sensitivity, are potential targets for chronic ethanol-induced adaptations. We have therefore examined N-methyl-d-aspartate (NMDA) receptors after chronic ethanol ingestion in rat lateral/basolateral amygdala.