Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: An update and future directions

• CeA circuitry is critical to alcoholism but the mechanisms are unclear.
• CRFRs mediate ethanol effects on CeA GABA and potentially glutamate transmission.
• Direct studies on ethanol effects on CeA CRF and non-CRF neurons are now emerging
• Here, we review some novel directions for CeA neurocircuit studies in alcoholism.
• Such new studies will be critical in development of novel treatments for alcoholism.

The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala. Work that is more recent suggests that corticotropin releasing factor also plays an important role in mediating anxiety-like behaviors via the enhancement of central amygdala glutamatergic transmission, implying that ethanol/corticotropin releasing factor interactions may modulate excitatory neurotransmission in this brain region. In addition, a number of studies utilizing optogenetic strategies or transgenic mouse lines have begun to examine specific central amygdala neurocircuit dynamics and neuronal subpopulations to better understand overall central amygdala neurocircuitry and the role of neuronal subtypes in mediating anxiety-like behaviors. This review will provide a brief update on this literature and describe some potential future directions that may be important for the development of better treatments for alcohol addiction.