UC San Diego
Alcohol Binge-Drinking on the Transition to Alcohol Dependence : Relationship and Neurobiological Basis
- Author(s): Kim, Sarah L.
- et al.
Intermittent access to alcohol in rats produces a pattern similar to alcohol binge drinking which has been shown to be associated with of alcohol dependence in humans, however direct causal evidence is missing. Moreover, the neuronal ensemble responsible for the excessive drinking behavior is currently unknown. The corticotropin-releasing factor (CRF) system in the central nucleus of the amygdala (CeA), an anti-reward stress brain system, has been speculated in playing a critical role during alcohol withdrawal. The aims of this set of studies were to test the causal effect of alcohol binge-drinking on the transition to alcohol dependence, and to test the causal role of recruitment of CeA neurons during withdrawal on alcohol drinking. To this end, we first measured the effect of a history of intermittent vs. continuous access to alcohol using a two-bottle choice paradigm on the motivation to drink in a model of alcohol dependence (chronic intermittent ethanol vapor exposure). We found that a history of intermittent access to alcohol accelerated the progression to alcohol dependence. We then tested whether withdrawal-dependent activation of Fos+ neurons in the CeA produces alcohol binge drinking behavior using the Daun02 inactivation method. Results showed that inactivation of Fos+ neurons decreased alcohol drinking both in binge-drinking rats and in dependent rats. These results demonstrate that a history of alcohol binge-drinking facilitates the transition to alcohol dependence and that recruitment of CeA neurons during withdrawal mediates excessive alcohol drinking