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Updated: May 14, 2026

Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF-R1
Jeffrey A Simms1, Carsten K Nielsen, Rui Li
1Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA, USA.
Abstract:
Corticotrophin-releasing factor (CRF) is a mediator of stress responses and a key modulator of ethanol-mediated behaviors. We report here that the CRF receptor 1 (CRF-R1) antagonist, CP-376395 reduces 20% ethanol consumption in animals trained to consume ethanol on an intermittent, but not a continuous, schedule. Furthermore, using [(35) S]GTPγS binding assays, we demonstrate that CRF-mediated G-protein signaling in the hypothalamus of the intermittent drinkers is decreased when compared to controls suggesting that the effects of CP-376395 are mediated by extrahypothalamic mechanisms. The present study provides further support for the use of CRF-R1 antagonists for the treatment of alcohol use disorders and suggests that ethanol consumption dysregulates CRF function in the hypothalamus.
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