The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice

Abstract

We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predis-posed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance.

Genetic Selection for Alcohol Preference in Mice Alters Dorsal Striatum Neurotransmission

“…These lines thus model divergent genetic predisposition for excessive alcohol intake and avoidance. HAP mice also exhibit other AUD‐relevant phenotypes relative to LAP mice such as heightened impulsivity (Oberlin and Grahame, ), enhanced alcohol tolerance capacity (Fritz and Boehm, ; Fritz et al., ), and a propensity for binge‐like alcohol consumption (Linsenbardt and Boehm, ). In selective breeding studies, these associated phenotypes are referred to as “correlated responses” to selection.…”

A multi‐omic analysis of the dorsal striatum in an animal model of divergent genetic risk for alcohol use disorder

“…An additional strength of this model is that HAP mice express other neurobehavioral phenotypes consistent with the clinical AUD description, thus increasing its translational validity. HAP mice exhibit a greater basal pharmacodynamic, but not pharmacokinetic, alcohol tolerance capacity relative to LAP mice and will drink alcohol to the point of both pharmacodynamic and pharmacokinetic tolerance development (Fritz & Boehm, 2014; Fritz et al., 2013). In addition, HAP mice are more impulsive than LAP mice (Oberlin & Grahame, 2009), develop sensitization to alcohol's psychomotor stimulating effects (Grahame et al., 2000), and demonstrate binge‐like alcohol consumption (Linsenbardt & Boehm, 2015).…”