Current studies in the BLA circuitry underlying

Current studies in the BLA circuitry underlying specific fear behaviors provide a framework for an improved understanding of the neurobiological underpinnings of alcohol use disorders and dependence. Notably, work on the specific alterations in amygdala microcircuitry produced by fear conditioning can act as a model and as a point of comparison with the effects of alcohol on amygdala circuitry. As fear conditioning and alcohol dependence can both be conceptualized as examples of aversive conditioning and can be measured in terms of learned behavior, they may engage the circuitry in the same way and produce similar effects at the cellular and whole animal level. Conversely, if conditioned fear is viewed as a useful physiological function and alcohol dependence is viewed as a maladaptive pathological process, then while they may engage the same microcircuitry, they will produce different (and possibly opposing) effects. This Ponceau S Staining Solution sale is supported by studies demonstrating increased GABA release following acute alcohol (Zhu & Lovinger, 2006) and decreased GABA levels following fear conditioning (Stork, Ji, & Obata, 2002). In addition, experimental evidence also indicates that binge-like alcohol exposure impairs fear conditioning in humans (Stephens et al., 2005) and that repeated alcohol withdrawal impairs the acquisition of fear conditioning in rats (Ripley, O\'Shea, & Stephens, 2003). However, it has also been shown that the retrieval of fear memory increased alcohol consumption in alcohol-withdrawn rats (Bertotto, Bussolino, Molina, & Martijena, 2010), suggesting that there may be some mechanisms for behavioral overlap. One potential point of overlap is the CRF and CRF1 system, which has been implicated in both fear conditioning and alcohol dependence. Fear-conditioned rats display increased CRF dialysate levels in the BLA that are positively correlated with the expression of fear behavior (Mountney, Anisman, & Merali, 2011). The CRF1 gene Crhr1 is upregulated in the BLA of dependent rats (Sommer et al., 2008), and selective deletion of the α1 GABAA receptor subunit in CRF+ neurons enhanced anxiety and impaired fear extinction (Gafford et al., 2012). Additionally, polymorphisms in the human crhr1 gene have been repeatedly associated with increased risk for alcoholism following stressful life events (Blomeyer et al., 2008, Ray et al., 2013, Schmid et al., 2010). The possible interference by alcohol on normal functioning of BLA microcircuitry adds a potential new layer to the existing knowledge on how alcohol alters normal brain function to contribute to the pathological phenotype of dependence. Impaired learning circuitry could explain why alcoholics continue to drink despite negative consequences, as well as why extinction therapy often fails in treating alcoholics. If chronic alcohol exposure alters amygdala circuitry that is critical for learned associations, then it could result in a compromised ability to process physiologically relevant negative associations and/or generate appropriate behavioral responses to aversive conditions.