Binge Drinking Decreases Corticotropin-Releasing Factor-Binding Protein Expression in the Medial Prefrontal Cortex of Mice.

Abstract

BACKGROUND:

Dysregulation of the corticotropin-releasing factor (CRF) system has been observed in rodent models of binge drinking, with a large focus on CRF receptor 1 (CRF-R1). The role of CRF-binding protein (CRF-BP), a key regulator of CRF activity, in binge drinking is less well understood. In humans, single-nucleotide polymorphisms in CRHBP are associated with alcohol use disorder and stress-induced alcohol craving, suggesting a role for CRF-BP in vulnerability to alcohol addiction.

METHODS:

The role and regulation of CRF-BP in binge drinking were examined in mice exposed to the drinking in the dark (DID) paradigm. Using in situ hybridization, the regulation of CRF-BP, CRF-R1, and CRF mRNA expression was determined in the stress and reward systems of C57BL/6J mice after repeated cycles of DID. To determine the functional role of CRF-BP in binge drinking, CRF-BP knockout (CRF-BP KO) mice were exposed to 6 cycles of DID, during which alcohol consumption was measured and compared to wild-type mice.

RESULTS:

CRF-BP mRNA expression was significantly decreased in the prelimbic (PL) and infralimbic medial prefrontal cortex (mPFC) of C57BL/6J mice after 3 cycles and in the PL mPFC after 6 cycles of DID. No significant changes in CRF or CRF-R1 mRNA levels were observed in mPFC, ventral tegmental area, bed nucleus of the stria terminalis, or amygdala after 3 cycles of DID. CRF-BP KO mice do not show significant alterations in drinking compared to wild-type mice across 6 cycles of DID.

CONCLUSIONS:

These results reveal that repeated cycles of binge drinking alter CRF-BP mRNA expression in the mPFC, a region responsible for executive function and regulation of emotion and behavior, including responses to stress. We observed a persistent decrease in CRF-BP mRNA expression in the mPFC after 3 and 6 DID cycles, which may allow for increased CRF signaling at CRF-R1 and contribute to excessive binge-like ethanol consumption.

• Authors: Kyle D Ketchesin, Gwen S Stinnett, Audrey F Seasholtz
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 40 Issue 8 Pg. 1641-50 (08 2016) ISSN: 1530-0277 [Electronic] England
• PMID: 27374820 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 by the Research Society on Alcoholism.

Chemical References

• Carrier Proteins
• Receptors, Corticotropin-Releasing Hormone
• corticotropin releasing factor-binding protein
• Ethanol
• CRF receptor type 1
• Corticotropin-Releasing Hormone

Topics

• Animals
• Binge Drinking (genetics, metabolism)
• Carrier Proteins (biosynthesis, genetics)
• Corticotropin-Releasing Hormone (biosynthesis, genetics)
• Ethanol (administration & dosage)
• Gene Expression
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Prefrontal Cortex (drug effects, metabolism)
• Receptors, Corticotropin-Releasing Hormone (biosynthesis, genetics)