INVESTIGATING THE EFFECTS OF THE CENTRAL NUCLEUS OF THE AMYGDALA (CEA) CORTICOTROPIN RELEASING FACTOR (CRF) AND CORTICOTROPIN RELEASING FACTOR TYPE 1 RECEPTOR (CRFR1) ON BINGE DRINKING BEHAVIOR AND THE TIME-DEPENDENT IMPACT OF ABSTINENCE AFTER BINGE

AUD is a neurobiological disorder that is characterized by compulsive alcohol use, this has numerous health, legal and economic consequences. One of the behaviors that has the largest consequence to suffer from AUD is alcohol binge drinking behavior. This behavior has distinct neuroanatomical and biological drivers. The Central Nucleus of the Amygdala (CeA), is our prime candidate region to control binge drinking behavior because of its known role for controlling anxiety and stress, known motivators of excessive alcohol use. The goal of this work, is to explore the role of the CeA in binge drinking behavior in genetic expression changes to differing periods of abstinence after binge drinking and the role of the CRF-CRFR1 system in binge drinking behavior, with a special interest in sex differences. Chapter 1, highlighted the fields findings and gaps with regards to the role of CeA and binge drinking behavior. Chapter 2, elucidated CeA gene expression changes of 25 genes of interest, during acute or protracted abstinence after binge drinking in both male and female mice, using qRT-PCR technology. Our results suggest that female mice during acute abstinence after Drinking in the Dark (DID) have upregulated of Gabra2 and Prcp while male mice had upregulated Sst, Npy, Npy2r and downregulated Grin1. During protracted abstinence female mice had downregulated relative gene expression of Crh and Npy, while male mice had upregulated relative gene expression of Npy2r, Npy and Sst. Chapter 3, explored the function of the CeA CRF-CRFR1 system in binge drinking behavior of both male and female mice. We use a targeted genetic deletion approach of neuronal CeA CRF or CRFR1 by infusing hSYN mediated Cre virus into the CeA of CRF or CRFR1 floxed mice. Our results suggest that CeA CRF deletion, overall reduced binge drinking in male mice while it increased drinking in female mice. Moreover, CeA CRFR1 genetic deletion did not alter binge drinking behavior. In conclusion, this thesis elucidates the role of the CeA in alcohol binge drinking behavior in the genetic and CRF-CRFR1 system perspective, highlighting the potential for more CeA targeted studies focused on binge drinking behavior and AUD.