Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF-R1 antagonist, CP-376395.
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.
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA, USA.
Jeffrey A
JA
Simms
Carsten K
CK
Nielsen
Rui
R
Li
Selena E
SE
Bartlett
D000428:Alcohol Drinking / Q000503:physiopathology*; D000631:Aminopyridines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D020318:Rats, Long-Evans
C529296:(3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine; D000631:Aminopyridines; D002492:Central Nervous System Depressants; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone
CP-376395; CRF; ethanol; hypothalamus; intermittent access