The Scripps Research Institute Alcohol Research Center

The Scripps Research Institute ARC

TSRI ARC

Featured Studies

TSRI-ARC Researchers Find Brain’s Alcohol Response ‘Switch’

New findings from Dr. Florence Varodayan in Dr. Marisa Roberto’s Lab (and in collaboration with Dr. Olivier George) have shown that the central amygdala (CeA) plays a critical role in the development of alcohol dependence. As a result, much preclinical alcohol research aims to identify relevant CeA neuroadaptions that promote the transition to dependence. Here we report that acute alcohol increases CeA neuronal activity in naïve rats by engaging L-type calcium channels (LTCCs) and that intra-CeA LTCC blockade reduces alcohol intake in non-dependent rats. Alcohol dependence disrupts this LTCC-based mechanism; instead, corticotropin-releasing factor type 1 receptors (CRF1s) mediate alcohol’s effects on CeA activity and drive the escalated alcohol intake of alcohol-dependent rats. This switch reflects the important role of the CeA in the pathophysiology of alcohol dependence and represents a new potential avenue for therapeutic intervention during the transition period. Schematic illustrating how the LTTC-based mechanism that mediates the CeA’s neuronal response to alcohol is altered with dependence, and the behavioral outcome of this neuroadaptation. A: In naïve/non-dependent rats, an LTCC-based mechanism governs: 1) alcohol’s enhancement of CeA action potential-dependent GABA release and 2) CeA-driven alcohol consumption. B: In alcohol-dependent rats, these alcohol-induced effects on CeA activity and escalated alcohol intake are mediated by a CRF1-based mechanism.