A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice

Michael Olive, Kristin K. Mehmert, Heather N. Koenig, Rosana Camarini, Joseph A. Kim, Michelle A. Nannini, Christine J. Ou, Clyde W. Hodge

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Rationale: Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans. Objective: The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone. Methods: Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm. Results: CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p. Conclusions: CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.

Original languageEnglish (US)
Pages (from-to)181-187
Number of pages7
JournalPsychopharmacology
Volume165
Issue number2
DOIs
StatePublished - 2003
Externally publishedYes

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Corticotropin-Releasing Hormone
Reward
Ethanol
Anxiety
Saccharin
Ideal Body Weight
Quinine
Water

Keywords

  • Conditioned place preference
  • Corticotropin releasing factor
  • Ethanol
  • Knockout mouse
  • Locomotor activity

ASJC Scopus subject areas

  • Pharmacology

Cite this

A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice. / Olive, Michael; Mehmert, Kristin K.; Koenig, Heather N.; Camarini, Rosana; Kim, Joseph A.; Nannini, Michelle A.; Ou, Christine J.; Hodge, Clyde W.

In: Psychopharmacology, Vol. 165, No. 2, 2003, p. 181-187.

Research output: Contribution to journalArticle

Olive, Michael ; Mehmert, Kristin K. ; Koenig, Heather N. ; Camarini, Rosana ; Kim, Joseph A. ; Nannini, Michelle A. ; Ou, Christine J. ; Hodge, Clyde W. / A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice. In: Psychopharmacology. 2003 ; Vol. 165, No. 2. pp. 181-187.
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abstract = "Rationale: Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans. Objective: The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone. Methods: Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm. Results: CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p. Conclusions: CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.",
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T1 - A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice

AU - Olive, Michael

AU - Mehmert, Kristin K.

AU - Koenig, Heather N.

AU - Camarini, Rosana

AU - Kim, Joseph A.

AU - Nannini, Michelle A.

AU - Ou, Christine J.

AU - Hodge, Clyde W.

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N2 - Rationale: Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans. Objective: The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone. Methods: Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm. Results: CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p. Conclusions: CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.

AB - Rationale: Corticotropin-releasing factor (CRF) plays an integral role in mediating stress responses and anxiety. However, little is known regarding the role of CRF in ethanol consumption, a behavior often associated with stress and anxiety in humans. Objective: The present study sought to determine the role of CRF in ethanol consumption, locomotor sensitivity and reward by examining these behaviors in C57BL/6J x 129S mice with a targeted disruption in the gene encoding the CRF prohormone. Methods: Male wild-type and CRF-deficient mice were given concurrent access to ethanol and water in both limited and unlimited-access two-bottle choice paradigms. Taste reactivity (saccharin or quinine vs water) was examined in a similar manner under continuous-access conditions. Blood ethanol levels and clearance were measured following limited ethanol access as well as a 4-g/kg i.p. injection of ethanol. Locomotor stimulant effects of ethanol were measured in an open-field testing chamber, and the rewarding effects of ethanol were examined using the conditioned place preference paradigm. Results: CRF-deficient mice displayed normal body weight, total fluid intake, taste reactivity and blood ethanol clearance, but consumed approximately twice as much ethanol as wild types in both continuous- and limited-access paradigms. CRF-deficient mice failed to demonstrate a locomotor stimulant effect following acute administration of ethanol (2 g/kg i.p.), and also failed to demonstrate a conditioned place preference to ethanol at 2 g/kg i.p., but did display such a preference at 3 g/kg i.p. Conclusions: CRF deficiency may lead to excessive ethanol consumption by reducing sensitivity to the locomotor stimulant and rewarding effects of ethanol.

KW - Conditioned place preference

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KW - Knockout mouse

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