Affective Behavior in Withdrawal Seizure–Prone and Withdrawal Seizure–Resistant Mice during Long-Term Alcohol Abstinence

Matthew C. Hartmann, Sarah E. Holbrook, Megan M. Haney, John Jr Crabbe, Alan M. Rosenwasser

Research output: Contribution to journalArticle

Abstract

Background: While the acute alcohol withdrawal syndrome has been well characterized both in human clinical studies and in experimental animals, much less is known regarding long-term affective disturbances that can sometimes persist during protracted abstinence. Nevertheless, since relapse often occurs long after acute detoxification and may be predicted by persistent affective disruption, a better understanding of the long-term behavioral consequences of prior alcohol dependence may lead to improved strategies for relapse prevention. Methods: Male and female Withdrawal Seizure–Prone and Withdrawal Seizure–Resistant mice from the second selection replicate (WSP-2, WSR-2) were exposed to a 10-day chronic-intermittent ethanol vapor protocol (CIE) or plain air and then tested repeatedly on the sucrose preference test (SPT), marble burying test (MBT), and the light–dark box test (LDT) over 7 weeks of (forced) abstinence. Results: While WSP and WSR mice differed significantly on tests of anxiety-like behavior (LDT, MBT), we found little evidence for long-term affective disruption following CIE in either line. The major exception was in the LDT, in that WSP but not WSR mice displayed longer latencies to enter the light compartment following CIE relative to air-controls. Conclusions: Selective breeding for acute withdrawal severity has resulted in differences in anxiety-like behavior between WSP and WSR mice. In contrast, however, genes contributing to the severity of acute withdrawal convulsions appear to have little overlap with those predisposing to affective disruption during long-term abstinence.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StatePublished - Jan 1 2019

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Alcohol Abstinence
Calcium Carbonate
Alcohols
Detoxification
Air
Sucrose
Animals
Ethanol
Anxiety
Genes
Vapors
Secondary Prevention
Alcoholism
Seizures
Light
Recurrence

Keywords

  • Affective Behavior
  • Chronic-Intermittent Ethanol
  • Protracted Abstinence
  • Withdrawal Seizure–Prone
  • Withdrawal Seizure–Resistant

ASJC Scopus subject areas

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

Cite this

Affective Behavior in Withdrawal Seizure–Prone and Withdrawal Seizure–Resistant Mice during Long-Term Alcohol Abstinence. / Hartmann, Matthew C.; Holbrook, Sarah E.; Haney, Megan M.; Crabbe, John Jr; Rosenwasser, Alan M.

In: Alcoholism: Clinical and Experimental Research, 01.01.2019.

Research output: Contribution to journalArticle

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N2 - Background: While the acute alcohol withdrawal syndrome has been well characterized both in human clinical studies and in experimental animals, much less is known regarding long-term affective disturbances that can sometimes persist during protracted abstinence. Nevertheless, since relapse often occurs long after acute detoxification and may be predicted by persistent affective disruption, a better understanding of the long-term behavioral consequences of prior alcohol dependence may lead to improved strategies for relapse prevention. Methods: Male and female Withdrawal Seizure–Prone and Withdrawal Seizure–Resistant mice from the second selection replicate (WSP-2, WSR-2) were exposed to a 10-day chronic-intermittent ethanol vapor protocol (CIE) or plain air and then tested repeatedly on the sucrose preference test (SPT), marble burying test (MBT), and the light–dark box test (LDT) over 7 weeks of (forced) abstinence. Results: While WSP and WSR mice differed significantly on tests of anxiety-like behavior (LDT, MBT), we found little evidence for long-term affective disruption following CIE in either line. The major exception was in the LDT, in that WSP but not WSR mice displayed longer latencies to enter the light compartment following CIE relative to air-controls. Conclusions: Selective breeding for acute withdrawal severity has resulted in differences in anxiety-like behavior between WSP and WSR mice. In contrast, however, genes contributing to the severity of acute withdrawal convulsions appear to have little overlap with those predisposing to affective disruption during long-term abstinence.

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