Alcohol use disorder (AUD) is a chronic disease that poses significant economic burden and health risks. It is pivotal to better understand brain mechanisms engaged by alcohol that promote misuse. The central amygdala (CeA) has emerged as a key mediator of excessive preclinical alcohol consumption. A dynorphin-expressing subpopulation within the CeA (CeA Dyn ) has been implicated in excessive alcohol drinking, yet how cellular activity of CeA Dyn neurons relates to ongoing alcohol drinking is not well-understood. The current study interrogated the engagement of CeA Dyn neurons in male and female mice during voluntary alcohol consumption using fiber photometry and compared this cellular response with that of other solutions having similar motivational and/or taste characteristics. Activity of a calcium sensor, GCaMP7f, expressed in mouse CeA Dyn neurons was recorded and time-locked to bouts of drinking. Multilevel linear mixed modeling was applied to better resolve focal effects from complex data. These analyses revealed a relatively large increase in CeA Dyn neuron calcium transients after bouts of alcohol drinking compared to water or sucrose drinking, indicating these neurons are uniquely engaged during alcohol consumption. Drinking behavior unique to alcohol (i.e., longer bout durations) did not fully explain signal differences between alcohol and other solutions nor did the relatively increased alcohol response diminish over time. No other conditions or solutions tested reproduced the pronounced change in CeA Dyn activity associated with alcohol drinking. These findings, collectively, support the presence of a unique functional signature for alcohol in a cell population known to control excessive alcohol drinking.
Highlights: Central amygdala dynorphin cells (CeA Dyn ) are firmly implicated in alcohol misuse. CeA Dyn neuron activity was higher when mice drank alcohol versus other solutions. Neither how mice drank alcohol nor motivational states could explain this activity. CeA Dyn neurons having uniquely high alcohol responses may underlie AUD development.