title: Binge Drinking Decreases Corticotropin-Releasing Factor-Binding Protein Expression in the Medial Prefrontal Cortex of Mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.|Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Ketchesin
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan.
authors.forename: Gwen S
authors.initials: GS
authors.lastname: Stinnett
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan.|Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Seasholtz
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D000099052:CRF Receptor, Type 1
chemical_list: D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Binge Drinking; CRF-Binding Protein; Corticotropin-Releasing Factor; Drinking in the Dark; Ethanol