Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice

Brandon M. Fritz, Kristy A. Cordero, Amanda M. Barkley-Levenson, Pamela Metten, John Jr Crabbe, Stephen L. Boehm

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance (AFT) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice (HDID-1) selectively bred for high blood EtOH concentrations (BECs) following limited access to EtOH in the Drinking in the Dark (DID) paradigm. Methods: Naïve male and female HDID-1 and HS/Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH-induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH-induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex (LORR). Results: HDID-1 mice exhibited reduced initial sensitivity to both EtOH-induced ataxia (p <0.001) and hypnosis (p <0.05) relative to HS/Npt mice. AFT was calculated by subtracting the BEC at loss of function from the BEC at recovery (Experiments 1 and 3) or by subtracting BEC at an initial recovery from the BEC at a second recovery following an additional alcohol dose (Experiment 2). The dowel test yielded no line differences in AFT, but HS/Npt mice developed slightly greater AFT to EtOH-induced LORR than HDID-1 (p <0.05). Conclusions: These results suggest that HDID-1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID, but do not display widely different development of AFT. These findings differ from previous findings with the high alcohol-preferring (HAP) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH-induced motor incoordination.

Original languageEnglish (US)
Pages (from-to)1284-1292
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Alcohol Drinking
Alcohols
Blood
Ataxia
Righting Reflex
Hypnosis
Hypnotics and Sedatives
Recovery
Experiments
Drinking
Genetic Predisposition to Disease
Ethanol

Keywords

  • Ataxia
  • High drinking in the dark mice
  • Loss of righting reflex
  • Selected mouse lines

ASJC Scopus subject areas

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

Cite this

Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice. / Fritz, Brandon M.; Cordero, Kristy A.; Barkley-Levenson, Amanda M.; Metten, Pamela; Crabbe, John Jr; Boehm, Stephen L.

In: Alcoholism: Clinical and Experimental Research, Vol. 38, No. 5, 2014, p. 1284-1292.

Research output: Contribution to journalArticle

Fritz, Brandon M. ; Cordero, Kristy A. ; Barkley-Levenson, Amanda M. ; Metten, Pamela ; Crabbe, John Jr ; Boehm, Stephen L. / Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice. In: Alcoholism: Clinical and Experimental Research. 2014 ; Vol. 38, No. 5. pp. 1284-1292.
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AU - Fritz, Brandon M.

AU - Cordero, Kristy A.

AU - Barkley-Levenson, Amanda M.

AU - Metten, Pamela

AU - Crabbe, John Jr

AU - Boehm, Stephen L.

PY - 2014

Y1 - 2014

N2 - Background: Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance (AFT) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice (HDID-1) selectively bred for high blood EtOH concentrations (BECs) following limited access to EtOH in the Drinking in the Dark (DID) paradigm. Methods: Naïve male and female HDID-1 and HS/Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH-induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH-induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex (LORR). Results: HDID-1 mice exhibited reduced initial sensitivity to both EtOH-induced ataxia (p <0.001) and hypnosis (p <0.05) relative to HS/Npt mice. AFT was calculated by subtracting the BEC at loss of function from the BEC at recovery (Experiments 1 and 3) or by subtracting BEC at an initial recovery from the BEC at a second recovery following an additional alcohol dose (Experiment 2). The dowel test yielded no line differences in AFT, but HS/Npt mice developed slightly greater AFT to EtOH-induced LORR than HDID-1 (p <0.05). Conclusions: These results suggest that HDID-1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID, but do not display widely different development of AFT. These findings differ from previous findings with the high alcohol-preferring (HAP) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH-induced motor incoordination.

AB - Background: Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance (AFT) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice (HDID-1) selectively bred for high blood EtOH concentrations (BECs) following limited access to EtOH in the Drinking in the Dark (DID) paradigm. Methods: Naïve male and female HDID-1 and HS/Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH-induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH-induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex (LORR). Results: HDID-1 mice exhibited reduced initial sensitivity to both EtOH-induced ataxia (p <0.001) and hypnosis (p <0.05) relative to HS/Npt mice. AFT was calculated by subtracting the BEC at loss of function from the BEC at recovery (Experiments 1 and 3) or by subtracting BEC at an initial recovery from the BEC at a second recovery following an additional alcohol dose (Experiment 2). The dowel test yielded no line differences in AFT, but HS/Npt mice developed slightly greater AFT to EtOH-induced LORR than HDID-1 (p <0.05). Conclusions: These results suggest that HDID-1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID, but do not display widely different development of AFT. These findings differ from previous findings with the high alcohol-preferring (HAP) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH-induced motor incoordination.

KW - Ataxia

KW - High drinking in the dark mice

KW - Loss of righting reflex

KW - Selected mouse lines

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