Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol

Abraham A. Palmer, Amanda L. Sharpe, Sue Burkhart-Kasch, Carrie S. McKinnon, Sarah C. Coste, Mary Stenzel-Poore, Tamara Phillips

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Rationale: Corticotropin-releasing factor (CRF) may play a significant role in drug and alcohol abuse. Objective: To evaluate the role of CRF in these processes, we examined several ethanol (EtOH) related behaviors in mice that carry a transgene that causes overexpression of CRF. Methods: We examined voluntary EtOH drinking, loss of the righting reflex (LORR), EtOH-induced conditioned taste aversion (CTA), and EtOH clearance in littermate transgenic (TG) and non-transgenic (non-TG) mice. In addition, because preliminary results indicated that age exacerbated differences in EtOH consumption between the two genotypes, we performed a cross-sectional and longitudinal evaluation of this trait at two ages (∼100 and 200 days old). Results: We found that TG mice consumed significantly less EtOH and had a lower preference for EtOH-containing solutions compared with their non-TG littermates. We also found that the older drug-naive TG mice drank less EtOH as compared with the younger mice of the same genotype; however, the same relationship did not exist for drug-naive non-TG mice. Prior experience in drinking EtOH when 100 days old led to decreased EtOH drinking when 200 days old in both genotypes. Duration of LORR was longer in the TG mice, EtOH-induced CTA was marginally greater in non-TG mice at the highest dose tested, and there were significant but small differences in EtOH clearance parameters. Conclusions: These data show that CRF overexpressing mice voluntarily consume less EtOH. This difference is associated with greater sensitivity to the sedative-hypnotic effects of EtOH, but not with increased sensitivity to the aversive effects of EtOH.

Original languageEnglish (US)
Pages (from-to)386-397
Number of pages12
JournalPsychopharmacology
Volume176
Issue number3-4
DOIs
StatePublished - Nov 2004

Fingerprint

Corticotropin-Releasing Hormone
Hypnotics and Sedatives
Drinking
Ethanol
Transgenic Mice
Righting Reflex
Genotype
Transgenes
Pharmaceutical Preparations
Alcoholism
Substance-Related Disorders

Keywords

  • Alcoholism
  • Corticotropin-releasing factor
  • Drinking
  • Ethanol
  • Genetic
  • Transgenic mice

ASJC Scopus subject areas

  • Pharmacology

Cite this

Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol. / Palmer, Abraham A.; Sharpe, Amanda L.; Burkhart-Kasch, Sue; McKinnon, Carrie S.; Coste, Sarah C.; Stenzel-Poore, Mary; Phillips, Tamara.

In: Psychopharmacology, Vol. 176, No. 3-4, 11.2004, p. 386-397.

Research output: Contribution to journalArticle

Palmer, Abraham A. ; Sharpe, Amanda L. ; Burkhart-Kasch, Sue ; McKinnon, Carrie S. ; Coste, Sarah C. ; Stenzel-Poore, Mary ; Phillips, Tamara. / Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol. In: Psychopharmacology. 2004 ; Vol. 176, No. 3-4. pp. 386-397.
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AU - Palmer, Abraham A.

AU - Sharpe, Amanda L.

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AU - McKinnon, Carrie S.

AU - Coste, Sarah C.

AU - Stenzel-Poore, Mary

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AB - Rationale: Corticotropin-releasing factor (CRF) may play a significant role in drug and alcohol abuse. Objective: To evaluate the role of CRF in these processes, we examined several ethanol (EtOH) related behaviors in mice that carry a transgene that causes overexpression of CRF. Methods: We examined voluntary EtOH drinking, loss of the righting reflex (LORR), EtOH-induced conditioned taste aversion (CTA), and EtOH clearance in littermate transgenic (TG) and non-transgenic (non-TG) mice. In addition, because preliminary results indicated that age exacerbated differences in EtOH consumption between the two genotypes, we performed a cross-sectional and longitudinal evaluation of this trait at two ages (∼100 and 200 days old). Results: We found that TG mice consumed significantly less EtOH and had a lower preference for EtOH-containing solutions compared with their non-TG littermates. We also found that the older drug-naive TG mice drank less EtOH as compared with the younger mice of the same genotype; however, the same relationship did not exist for drug-naive non-TG mice. Prior experience in drinking EtOH when 100 days old led to decreased EtOH drinking when 200 days old in both genotypes. Duration of LORR was longer in the TG mice, EtOH-induced CTA was marginally greater in non-TG mice at the highest dose tested, and there were significant but small differences in EtOH clearance parameters. Conclusions: These data show that CRF overexpressing mice voluntarily consume less EtOH. This difference is associated with greater sensitivity to the sedative-hypnotic effects of EtOH, but not with increased sensitivity to the aversive effects of EtOH.

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