Marisa Roberto, Sophia Kohm, Dean Kirson, Michal Bajo, Christopher Oleata and Florence Varodayan
Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037
Gamma-aminobutyric acid (GABAergic) transmission in the central amygdala (CeA) is critical to the development of alcohol use disorders, and the physiological response to stressors. Accumulating evidence indicates that alcohol abuse and stress induce neuroadaptations in brain stress-related peptide systems and these functional alterations in the CeA are in part responsible for some of the behavioral and physiological phenotypes associated with anxiety and alcohol dependence.
The goal of this talk is to highlight recent electrophysiological studies exploring the roles of stress-related peptides, such as corticotropin releasing factor (CRF), substance P (SP) as well as anti-stress peptides, nociceptin/orphanin FQ and oxytocin (OT), on GABAergic transmission in the CeA.
CRF release is increased in the CeA during withdrawal in alcohol-dependent animals and contributes to withdrawal-related anxiety and increased alcohol consumption in dependent animals. Many of the anti-stress peptides within the CeA are implicated in regulating voluntary ethanol intake, participate in the response to acute stress exposure and exert a marked antagonist effects on the CRF system. We have shown that these neuropetidergic-GABA interactions in the CeA undergo adaptive changes with ethanol dependence and stress restraint, supporting their recruitment during the development of alcohol dependence and anxiety disorders.
Understanding the cellular mechanisms of neuropepetides and their role in modulating GABAergic signaling will uncover key neuroadaptive targets and provide insight into the transition to addiction and anxiety-disorders, as well as into possible treatment.
Supported by grants from NIAAA: AA015566, AA06420, AA017447, AA021491 and AA013498 and from the Pearson Center for Alcoholism and Addiction Research.