Effects of chronic ethanol withdrawal on the amygdala

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DESCRIPTION (provided by applicant): A significant factor that influences alcoholics to continue to abuse alcohol is the severe anxiety experienced during withdrawal. The neurobiological mechanisms governing these long-lasting alterations in anxiety are currently unknown. Within the brain, the amygdala is a major emotional epicenter and regulates the expression of both learned-fear and anxiety. Preliminary data from our lab has shown that there are changes in glutamatergic transmission in the lateral amygdala/basolateral amygdala (BLA) synapses with chronic ethanol and withdrawal. Glutamate receptors, particularly AMPA-type and potentially kainite-type receptors (Li et al., 2001), play a major role in long-term synaptic alterations within the amygdala. However, we do not know if these receptors are associated with the long-term anxiogenic effects of alcohol withdrawal in the external capsule (EC)/BLA synapses. The current application will address the central hypothesis that withdrawal from chronic ethanol will differentially alter AMPA- and kainate-mediated glutamatergic transmission at EC/BLA synapses in a manner similar to fear learning.