Binge Drinking Decreases Corticotropin‐Releasing Factor‐Binding Protein Expression in the Medial Prefrontal Cortex of Mice
| Autor: | Audrey F. Seasholtz, Gwen S. Stinnett, Kyle D. Ketchesin |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty Corticotropin-Releasing Hormone Gene Expression Prefrontal Cortex Medicine (miscellaneous) Binge drinking In situ hybridization Alcohol use disorder Biology Toxicology Receptors Corticotropin-Releasing Hormone Amygdala Article Binge Drinking Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Prefrontal cortex Mice Knockout Ethanol medicine.disease Mice Inbred C57BL Ventral tegmental area Psychiatry and Mental health Stria terminalis 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Carrier Proteins hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | Alcoholism: Clinical and Experimental Research. 40:1641-1650 |
| ISSN: | 1530-0277 0145-6008 |
| DOI: | 10.1111/acer.13119 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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