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Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF ‐ R1 antagonist, CP ‐376395
Author(s) -
Simms Jeffrey A.,
Nielsen Carsten K.,
Li Rui,
Bartlett Selena E.
Publication year - 2014
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12024
Subject(s) - antagonist , endocrinology , hypothalamus , medicine , ethanol , chemistry , receptor , biochemistry
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.