Pharmacogenetic and optogenetic control of alcohol dependence through inactivation of a withdrawal neuronal ensemble in the central amygdala.

Sandra Helinski

George O
The Scripps Research Institute, La Jolla, CA, USA

A neuronal ensemble in the central nucleus of the amygdala (CeA) that is recruited in anticipation of alcohol binge drinking has been recently identified but causal evidence that this “binge-drinking” neuronal ensemble is responsible for alcohol binge drinking is lacking. Moreover, unknown are whether a “dependence” neuronal ensemble can also be identified in the CeA in dependent rats and whether this hypothetical dependence neuronal ensemble is responsible for compulsive-like alcohol drinking in dependent rats. We tested the hypothesis that there are specific neuronal ensembles in the CeA that are responsible for alcohol binge-like drinking, compulsive-like drinking and emergence of somatic signs of withdrawal using pharmacogenetics (cfos-lacZ/Daun02 inactivation) and optogenetics (crh-Cre/Halorhodopsin approaches. Results show that the recruitment of a neuronal ensemble in the CeA during alcohol withdrawal is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributes to alcohol binge drinking in nondependent rats. These results identify a critical neurobiological mechanism that is responsible for alcohol dependence, suggesting that targeting the dependence-induced neuronal ensembles in the amygdala may lead to more effective medications for the treatment of alcoholism.