CRF1 Receptor Signaling Regulates Food and Fluid Intake in the Drinking-in-the-Dark Model of Binge Alcohol Consumption
Article first published online: 7 FEB 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 7, pages 1161–1170, July 2013
How to Cite
Giardino, W. J. and Ryabinin, A. E. (2013), CRF1 Receptor Signaling Regulates Food and Fluid Intake in the Drinking-in-the-Dark Model of Binge Alcohol Consumption. Alcoholism: Clinical and Experimental Research, 37: 1161–1170. doi: 10.1111/acer.12076
- Issue published online: 3 JUL 2013
- Article first published online: 7 FEB 2013
- Manuscript Accepted: 30 NOV 2012
- Manuscript Received: 30 AUG 2012
- NIH. Grant Numbers: F31 AA021023, AA013738, AA016647, AA010760, NBI-27914
Several recent studies implementing the standard “drinking-in-the-dark” (DID) model of short-term binge-like ethanol (EtOH) intake in C57BL/6J mice highlighted a role for the stress-related neuropeptide corticotropin-releasing factor (CRF) and its primary binding partner, the CRF type-1 (CRF1) receptor.
We evaluated the selectivity of CRF1 involvement in binge-like EtOH intake by interrupting CRF1 function via pharmacological and genetic methods in a slightly modified 2-bottle choice DID model that allowed calculation of an EtOH preference ratio. In addition to determining EtOH intake and preference, we also measured consumption of food and H2O during the DID period, both in the presence and absence of EtOH and sweet tastant solutions.
Treatment with either of the CRF1-selective antagonists CP-376,395 (CP; 10 to 20 mg/kg, i.p.) or NBI-27914 (10 to 30 mg/kg, i.p.) decreased intake of 15% EtOH in male C57BL/6J mice, but did so in the absence of a concomitant decrease in EtOH preference. These findings were replicated genetically in a CRF1 knockout (KO) mouse model (also on a C57BL/6J background). In contrast to effects on EtOH intake, pharmacological blockade of CRF1 with CP increased intake of 10% sucrose, consistent with previous findings in CRF1 KO mice. Finally, pharmacological and genetic disruption of CRF1 activity significantly reduced feeding and/or total caloric intake in all experiments, confirming the existence of nonspecific effects.
Our findings indicate that blockade of CRF1 receptors does not exert specific effects on EtOH intake in the DID paradigm, and that slight modifications to this procedure, as well as additional consummatory control experiments, may be useful when evaluating the selectivity of pharmacological and genetic manipulations on binge-like EtOH intake.