Corticotropin releasing factor, but not alcohol, modulates norepinephrine release in the rat central nucleus of the amygdala. (15th November 2020)

• Record Type: Journal Article
• Authors: Hedges, David M.; Yorgason, Jordan T.; Brundage, James N.; Wadsworth, Hillary A.; Williams, Benjamin; Steffensen, Scott C.; Roberto, Marisa
• Is Part Of: Neuropharmacology. Volume 179(2020)
• Publication Date: 2020-11-15
• Subjects: Stress -- Alcohol -- CRF -- Norepinephrine -- Amygdala -- Voltammetry; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2020.108293
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Alcohol misuse and dependence is a widespread health problem. The central nucleus of the amygdala (CeA) plays important roles in both the anxiety associated with alcohol (ethanol) dependence and the increased alcohol intake that is observed during withdrawal in dependent animals. We and others have shown the essential involvement of the corticotropin releasing factor (CRF) system in alcohol's synaptic effects on the CeA and in the development of ethanol dependence. Another system that has been shown to be critically involved in the molecular underpinnings of alcohol dependence is the norepinephrine (NE) system originating in the locus coeruleus. Both the CRF and NE systems act in concert to facilitate a stress response: central amygdalar afferents release CRF in the locus coeruleus promoting widespread release of NE. In this study, we are the first to use fast-scan cyclic voltammetry to classify local electrically-evoked NE release in the CeA and to determine if acute alcohol and CRF modulate it. Evoked NE release is action potential dependent, is abolished after depletion of monoaminergic vesicles, differs pharmacologically from dopamine release, is insensitive to acute alcohol, and decreases in response to locally applied CRF. Taken together, these results indicate that NE release in the CeA is released canonically in a vesicular-dependent manner, and that while acute alcohol does not directly alter NE release, CRF decreases it. Our results suggest that CRF acts locally on NE terminals as negative feedback and potentially prevents hyperactivation of the CRF-norepinephrine stress pathway. Highlights: Evoked norepinephrine release in the CeA is vesicle and action potential dependent. CRF decreases norepinephrine release in the CeA. Norepinephrine release in the CeA is insensitive to alcohol.