Ethanol Tolerance of Cerebellar Purkinje Neurons from Selectively Outbred Mouse Lines: in Vivo and in Vitro Electrophysiological Investigations

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Abstract
The electrophysiological activity of cerebellar Purkinje neurons was characterized in long sleep (LS: ethanol sensitive) and short sleep (SS: ethanol insensitive) mice made tolerant to ethanol. After 1 to 4 weeks of feeding on a liquid ethanol diet, mice of both lines were less sensitive to the sedative and ataxic effects of parenteral ethanol than were controls. In addition, cerebellar Purkinje cells in ethanol-fed LS and SS mice were less responsive than the controls to the depressant effects of ethanol applied via bath perfusion in vitro and via local pressure ejection application in vivo. Tolerance to the electrophysiological effects of ethanol were already apparent after 7 to 9 days on the ethanol diet, and the degree of tolerance did not increase significantly in either mouse line fed ethanol for an additional 1–3 weeks. Finally, the differences in ethanol sensitivities of naive mice (LS >> SS) were maintained following the development of tolerance. We conclude that tolerance to both the cellular and behavioral depressant effects of ethanol can be observed after chronic feeding with ethanol in LS and SS mice, and that there are no significant differences in the degree of tolerance developed by these mice. In addition, our data suggest that the inherited differences in ethanol sensitivity between LS and SS mice, and the changes in ethanol sensitivity which occur in these mice with chronic exposure to this depressant agent, are mediated by different mechanisms.