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

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 occu...

Full description

Saved in:
Bibliographic Details
Published in:Alcoholism, clinical and experimental research clinical and experimental research, 2019-07, Vol.43 (7), p.1478-1485
Main Authors: Hartmann, Matthew C., Holbrook, Sarah E., Haney, Megan M., Crabbe, John C., Rosenwasser, Alan M.
Format: Article
Language:English
Subjects:
Abstinence
Affective Behavior
Alcohol use
Alcohol withdrawal
Alcoholism
Alcohols
Anxiety
Chronic‐Intermittent Ethanol
Convulsions
Convulsions & seizures
Dependence
Detoxification
Disruption
Drug dependence
Emotional behavior
Ethanol
Mice
Protracted Abstinence
Selective breeding
Sucrose
Sugar
Withdrawal Seizure–Prone
Withdrawal Seizure–Resistant
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Suggestive evidence that Withdrawal Seizure‐Prone (WSP) mice exhibit greater and/or more persistent anxiety‐like behavior in the light‐dark box test following chronic‐intermittent EtOH vapor exposure relative to Withdrawal Seizure‐Resistant (WSR) mice. 40% of EtOH‐exposed WSP mice failed to emerge from the dark compartment on at least one post‐Tx day, compared to 5% of EtOH‐exposed WSR, 15% of air‐exposed WSP, and 0% of air‐exposed WSR. These data offer a tentative link between genetic predisposition to acute withdrawal severity and abstinenceinduced anxiety‐like behavior.
ISSN:0145-6008
1530-0277
DOI:10.1111/acer.14074