Binge alcohol consumption is a severe public health problem and is the third leading cause of preventable death in the USA (Hingson et al., 2005; 2007). Defining the neural circuitry that modulates excessive binge alcohol intake is essential for developing effective therapeutics to treat this disease. Corticotropin releasing factor (CRF) is an important neuropeptide, in regards to binge alcohol consumption as peripheral and site- specific administrations of CRF antagonists can reduce excessive ethanol intake (Sparta et al., 2008; 2009; 2013). While CRF is found throughout the brain, the extended amygdala consisting of the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) CRF projections the to ventral tegmental area (VTA) remain a particularly interesting candidate targets for CRF?s modulation of binge drinking, since these structures provide direct connections from stress to reward brain regions I hypothesize that binge alcohol exposure leads to an increase of extended amygdalar CRF neuronal drive onto VTA GABA neurons. Specifically, I hypothesize that the CRF CeA to VTA projection is recruited during repeated binge drinking sessions, whereas the CRF BNST to VTA pathway is involved with the initiation of binge drinking. To test these hypotheses, I will utilize optogenetics, in vivo electrophysiology, ex vivo patch clamp, and behavior. Taken together, this proposal will provide a thorough characterization of both the CeA-and BNST-VTA CRF neural circuits after binge alcohol intake and may identify possible pharmacological targets for the treatment of alcoholism.
Binge alcohol consumption has a significant impact on the health of the individual in society. The research generated in this proposal will investigate specific limbic to reward circuits that modulate binge drinking. These data will shed light on the neurobiological mechanisms underlying binge ethanol drinking, as well as the identification of novel circuit nodes that may be targeted for pharmacological treatment.
