Young investigators stress alcohol-induced neuroadaptations in extended amygdala

摘要

Excessive alcohol use, alcohol abuse, and relapse to heavy drinking are all characteristic of alcohol use disorders. Brain circuits controlling reward, appetitive behavior, decision making and habit formation have been implicated in these aspects of alcohol seeking and intake in a variety of animals. A number of studies over the past 10-15 years have also generated evidence that brain circuits implicated in stress responsiveness also regulate alcohol drinking behavior (reviewed in Breese, Sinha, & Heilig, 2011; Heinz, Beck, Grusser, Grace, & Wrase, 2009; Koob, 2009; Silberman et al., 2009; Vengeliene, Bilbao, Molander, & Spanagel, 2008). The extended amygdala, a series of interconnected limbic brain nuclei that includes (among other regions) the nucleus accumbens, central amygdala and bed nucleus of the stria terminalis (BNST) has emerged as a circuit key to the interface of stress- and alcohol-related behaviors. Interactions of these brain regions with "limbic" cortical areas provide influences from brain circuitry involved in context recognition, affective control and decision making. Thus, the extended amygdala is poised to integrate an array of environ-mentar information that can influence alcohol-related behaviors. In addition, evidence of direct alcohol effects on this circuitry has emerged from studies using animal models. Overall, this circuit is most strongly linked to alcohol intake driven by the need to relieve negative outcomes of abstinence/withdrawal following a history of alcohol consumption. Withdrawal itself is stressful, and can also be impacted by stressful environmental events. Studies in several laboratories are now focusing on how stress, past drinking history and the extended amygdala circuitry contribute to relapse to drinking in rodent models.