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  • Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF-R1 antagonist, CP-376395.

Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF-R1 antagonist, CP-376395.

Addiction biology (2013-02-01)
Jeffrey A Simms, Carsten K Nielsen, Rui Li, Selena E Bartlett
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.

MATERIALS
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Product Description

Sigma-Aldrich
CP-376395 hydrochloride, ≥98% (HPLC)