Selection for high alcohol preference drinking in mice results in heightened sensitivity and rapid development of acute functional tolerance to alcohol's ataxic effects

• Published in: Genes, brain and behavior brain and behavior, 2013-02, Vol.12 (1), p.78-86
• Main Authors: Fritz, B. M., Grahame, N. J., Boehm, S. L.
• Format: Article
• Language: English
• Subjects: Addiction; Addictive behaviors; Adult and adolescent clinical studies; Alcohol; Alcohol Drinking - genetics; Alcoholic Intoxication - genetics; Alcoholism; Alcoholism - genetics; Alcoholism and acute alcohol poisoning; Animals; ataxia; behavior; Behavior, Animal - drug effects; Biological and medical sciences; Ethanol; Ethanol - blood; Ethanol - toxicity; Experiments; Female; Gait Ataxia - chemically induced; Gait Ataxia - genetics; Genetic Predisposition to Disease; genetics; Male; Medical research; Medical sciences; Mice; Mice, Inbred Strains; mouse; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rodents; selected lines; Selection, Genetic; sensitivity; Species Specificity; tolerance; Toxicology
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/j.1601-183X.2012.00830.x

Selectively‐bred high alcohol‐preferring mice are significantly more sensitive to alcohol's ataxic effects and develop more rapid acute functional tolerance than low alcohol‐preferring mice. Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of this study was to assess this potential correlated response between alcohol preference and AFT in second and third replicate lines of mice selectively bred for high (HAP2 and HAP3) and low (LAP2 and LAP3) alcohol preference drinking. Male and female mice were tested for development of AFT on a static dowel task, which requires that animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse received one (1.75 g/kg; Experiment 1) or two (1.75 and 2.0 g/kg; Experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in Experiment 2, an additional administration after the first regain of balance on the dowel. Blood samples were taken immediately after loss of balance [when blood ethanol concentrations (BECs) were rising] and at recovery (during falling BECs) in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial injection of ethanol and were therefore more sensitive to its early effects. Furthermore, Experiment 1 detected significantly greater AFT development (BECfalling − BECrising) in HAP mice when compared with LAP mice, which occurred within ∼30 min, supporting our hypothesis. However, AFT was not different between lines in Experiment 2, indicating that ∼30–60 min following alcohol administration, AFT development was similar in both lines. These data show that high alcohol drinking genetically associates with both high initial sensitivity and very early tolerance to the ataxic effects of ethanol.