An automated attentional set-shifting task in HAP, LAP, and alcohol-exposed cHAP mice

Abstract

Alcoholics often experience difficulties ceasing drinking, potentially related to excessive behavioral inflexibility that either precedes or results from high alcohol consumption. Components of the Wisconsin Card-Sorting Task (WCST) a type of Attentional Set-Shifting (AttSS) task measuring impairments in behavioral flexibility have been modified to measure similar constructs within animals. Previous work has shown impaired AttSS in abstinent alcoholics and nonalcoholic individuals with a family history of alcoholism, as well as in mice exposed to chronic-intermittent alcohol vapor (Gierski et al., 2013; Hu et al., 2015; Oscar-Berman et al., 2009). The aim of the current study was to assess whether selectively-bred High- vs. Low- Alcohol Preferring (HAP vs LAP) mice display behavioral inflexibility as measured by an operant AttSS task, and furthermore, whether a history of voluntary drinking in cross-bred HAP (cHAP) mice further increases inflexibility. Impairments in the AttSS task are assessed by evaluating the number of trials to reach criterion, as well as the number and types of errors committed during the second experimental phase. In Experiment 1, male and female HAP and LAP mice first learned to press one of two levers signaled by a visual cue, but random with respect to spatial orientation, for a 0.1% saccharin solution reward. The following experimental phase consisted of an egocentric discrimination, such that side (left or right) now signaled correct reinforcement and the location of the visual cue was irrelevant. In Experiment 2, prior to identical operant procedures as Experiment 1, male and female cHAP mice were given free-choice access to 10% alcohol or water for seven weeks. Ethanol-exposed animals drank an average of 29.6 g/kg/day.