Corticotropin-Releasing Factor Acting on Corticotropin-Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice

Simranjit Kaur, Ju Li, Mary Stenzel-Poore, Andrey Ryabinin

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39 Citations (Scopus)

Abstract

Background: The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access "drinking in the dark" (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm. Methods: On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. Results: CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs. Conclusions: Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.

Original languageEnglish (US)
Pages (from-to)369-376
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume36
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Corticotropin-Releasing Hormone Receptors
Binge Drinking
Corticotropin-Releasing Hormone
Urocortins
Knockout Mice
Alcohol Drinking
Alcohols
Ethanol
Drinking
Sucrose
Ligands
Blood
CRF receptor type 1
Water

Keywords

  • Alcoholism
  • Corticotropin-Releasing Hormone
  • Ethanol Drinking
  • Limited Access
  • Stress

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

@article{1a65df920f7447f1b456f57dfbd847c7,
title = "Corticotropin-Releasing Factor Acting on Corticotropin-Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice",
abstract = "Background: The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access {"}drinking in the dark{"} (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm. Methods: On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20{\%} ethanol or 10{\%} sucrose for 2hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. Results: CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs. Conclusions: Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.",
keywords = "Alcoholism, Corticotropin-Releasing Hormone, Ethanol Drinking, Limited Access, Stress",
author = "Simranjit Kaur and Ju Li and Mary Stenzel-Poore and Andrey Ryabinin",
year = "2012",
month = "2",
doi = "10.1111/j.1530-0277.2011.01610.x",
language = "English (US)",
volume = "36",
pages = "369--376",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
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T1 - Corticotropin-Releasing Factor Acting on Corticotropin-Releasing Factor Receptor Type 1 is Critical for Binge Alcohol Drinking in Mice

AU - Kaur, Simranjit

AU - Li, Ju

AU - Stenzel-Poore, Mary

AU - Ryabinin, Andrey

PY - 2012/2

Y1 - 2012/2

N2 - Background: The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access "drinking in the dark" (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm. Methods: On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. Results: CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs. Conclusions: Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.

AB - Background: The corticotropin-releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate alcohol intake in the limited access "drinking in the dark" (DID) model of binge drinking. To avoid the potential nonspecific effects of antagonists, in this study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO and corresponding wild-type (WT) littermates using the DID paradigm. Methods: On days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT littermates were provided with 20% ethanol or 10% sucrose for 2hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4hours. At the end of each drinking session, the volume of ethanol consumed was recorded, and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. Results: CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared with WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared with WTs. Conclusions: Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption.

KW - Alcoholism

KW - Corticotropin-Releasing Hormone

KW - Ethanol Drinking

KW - Limited Access

KW - Stress

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