External inhibition of ethanol tolerance

Abstract

<p>According to a conditioning analysis of tolerance, pharmacological conditional responses (CRs) contribute to tolerance. It has previously been reported that, as expected on the basis of this model, tolerance to the hypothermic effect of ethanol is attenuated by "external inhibition" i.e., by the presentation of a novel stimulus (a strobe light). However, results of more recent research indicate that novel stimuli augment the hypothermic effect of ethanol in rats receiving the drug for the first time. It is possible, therefore, that a novel stimulus apparently attenuates ethanol tolerance because it augments ethanol-hypothermia, rather than because it functions as an external inhibitor. Results presented in this thesis confirm reports that ethanol-induced hypothermia is augmented by a novel stimulus, thus prior demonstrations of external inhibition of ethanol tolerance is equivocal. Further experiments in this thesis evaluated external inhibition tolerance to another effect of ethanol--ataxia. Although the initial ataxic effect of ethanol (unlike the hypothermic effect) is not enhanced by a novel stimulus (a strobe light/white noise combination), the stimulus reinstated ethanol-induced ataxia in tolerant rats. Tolerance was also disrupted by the novel omission of the strobe/noise stimulus. Thus, experiments in this thesis demonstrate external inhibition of ethanol tolerance in a preparation not confounded by the effects of the novel stimulus on initial responding to ethanol. Experiments reported in this thesis also demonstrate that tolerance to the ataxic effect of ethanol is mediated by a compensatory CR, termed "hypertaxia." The compensatory CR was disrupted by the novel addition and novel omission of the strobe/noise stimulus providing converging evidence that the attention of tolerance by a novel stimulus results from external inhibition of Pavlovian conditioning. Finally, external inhibition of ethanol tolerance was not evident when there was a long delay between tolerance development sessions and testing. These data are consistent with an associative analysis of tolerance which suggests that contextual control of tolerance should be minimized as the interval between training and testing is increased.</p>