Ataxia and c-Fos Expression in Mice Drinking Ethanol in a Limited Access Session

Authors

  • Amanda L. Sharpe,

    Corresponding author
    1. From Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon.
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  • Natalia O. Tsivkovskaia,

    1. From Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon.
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  • Andrey E. Ryabinin

    1. From Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon.
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Amanda L. Sharpe, Oregon Health and Science University, Department of Behavioral Neuroscience, L470, 3181 SW Sam Jackson Park Road, Portland, OR 97239; Fax: 503-494-6877; E-mail: sharpea@ohsu.eduy

Abstract

Background:

Although previous murine studies have demonstrated ethanol self-administration resulting in blood ethanol concentrations (BECs) believed to be pharmacologically relevant, to our knowledge, no study reported to date has demonstrated intoxication via ataxia after self-administration. Thus, the goal of this study was to demonstrate ataxia and to examine changes in c-Fos expression in mice after self-administration of intoxicating doses of ethanol.

Methods:

Male C57BL/6J mice were trained to drink a 10% ethanol solution during daily 30-min limited access sessions. Mice were exposed to increasing concentrations of ethanol until a 10% ethanol solution was reached. BEC and ataxia, measured as foot slips off of a balance beam, were examined after the limited access self-administration session. In a separate experiment, various brain structures from mice drinking water or ethanol were examined for changes in c-Fos expression two hr after the limited access session.

Results:

Mice drank between 1.5 and 2 g/kg of 10% ethanol during the daily 30-min session. BECs for these mice 15 min after the limited access session ranged between 0.52 and 2.13 mg/ml. A significant increase in foot slips off a balance beam was seen immediately after ethanol consumption during the limited access session. Among mice drinking ethanol, an increase in c-Fos expression was seen in the Edinger-Westphal nucleus, and a decrease in c-Fos expression was seen in the cingulate cortex, ventral tegmental area, lateral and medial septum, CA1 region of the hippocampus, and basolateral amygdala.

Conclusions:

After this procedure in mice, BECs are achieved that are in a range considered pharmacologically relevant and intoxicating. Significant ataxia was observed after ethanol self-administration. Brain regions showing changes in c-Fos expression after voluntary intoxication were similar to those previously reported, suggesting that these brain regions are involved in regulating behavioral effects of alcohol intoxication.

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