The influence of selection for ethanol withdrawal severity on traits associated with ethanol self-administration and reinforcement

Abstract

Background: Several meta-analyses indicate that there is an inverse genetic correlation between ethanol preference drinking and ethanol withdrawal severity, but limited work has characterized ethanol consumption in 1 genetic animal model, the Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mouse lines selected for severe or mild ethanol withdrawal, respectively.

Methods: We determined whether line differences existed in: (i) operant self-administration of ethanol during sucrose fading and under different schedules of reinforcement, followed by extinction and reinstatement of responding with conditioned cues and (ii) home cage drinking of sweetened ethanol and the development of an alcohol deprivation effect (ADE).

Results: Withdrawal Seizure-Prone-1 mice consumed more ethanol than WSR-1 mice under a fixed ratio (FR)-4 schedule as ethanol was faded into the sucrose solution, but this line difference dissipated as the sucrose was faded out to yield an unadulterated 10% v/v ethanol solution. In contrast, WSR-1 mice consumed more ethanol than WSP-1 mice when a schedule was imposed that procedurally separated appetitive and consummatory behaviors. After both lines achieved the extinction criterion, reinstatement was serially evaluated following oral ethanol priming, light cue presentation, and a combination of the 2 cues. The light cue produced maximal reinstatement of responding in WSP-1 mice, whereas the combined cue was required to produce maximal reinstatement of responding in WSR-1 mice. There was no line difference in the home cage consumption of a sweetened ethanol solution over a period of 1 month. Following a 2-week period of abstinence, neither line developed an ADE.

Conclusions: Although some line differences in ethanol self-administration and reinstatement were identified between WSP-1 and WSR-1 mice, the absence of consistent divergence suggests that the genes underlying these behaviors do not reliably overlap with those that govern withdrawal severity.