Date of Award
Doctor of Philosophy (PhD)
Professor Shepard Siegel
Some studies have demonstrated that the effects of a drug may be different, depending on whether the drug is self-administered or passively received by the subject. Most of the studies which have examined this phenomenon have not examined the effects of a drug following each of a series of administrations. Moreover, the mechanism mediating differences between self-administered and passively received drugs has not been determined. The present experiments used a yoked-control design to examine the development of tolerance to the ataxic effects of heroin and of ethanol in rats that self-administer the drugs and rats that passively received them. Results demonstrate that rats that passively received heroin, but not those that self-administered the drug, were significantly impaired following the initial administrations. During the first administration sessions, rats that self-administered ethanol were as impaired as their partners that passively received, but within a few sessions self-administering rats developed tolerance to the ataxic effect of the ethanol, while their yoked partners did not. The results also suggest that the faster tolerance development in rats that self-administered ethanol may have been mediated by differences in Pavlovian conditioning in these subjects, which demonstrated larger compensatory conditional responses in the form of "hypertaxia" than did their yoked partners. The results indicated that some component of the self-administration process contributed to the Pavlovian conditioning, and hence, faster tolerance development, of self-administering animals. The data suggest that studies in which drugs are passively received may overestimate the dose that is necessary to produce tolerance in self-administering animals. Models based on such studies, then, may require modification before they are applied to situations which involve self-administration of drugs.
Weise-Kelly, Lorraine Ann, "Drug-induced ataxia: Effect of the self-administration contingency" (1999). Open Access Dissertations and Theses. Paper 1796.