Abstract
Spontaneous locomotor activity has been used to assess the development and the dissipation of tolerance to nicotine in rats. Nicotine administered i.p. to experimentally naive rats depressed activity in a Y-shaped runway in a dose-related manner. After a single i.p. dose of nicotine, acute tolerance to the depressant action of a second dose developed with a definite time-course, becoming maximal after 2 h and wearing off after about 8 h. Repeated i.p. doses of nicotine (3 times daily for 8 days) elicited chronic tolerance, which was found to persist for at least 90 days after the end of regular treatment with the drug. Tolerance was also produced when nicotine was administered in rats' drinking water and through reservoirs implanted subcutaneously. We conclude that tolerance to nicotine in rats can develop quickly, may be measured easily, and persists for prolonged periods after withdrawal. A nicotine abstinence syndrome was not detected. The doses (mg/kg i.p.) of nicotine necessary to induce chronic tolerance in rats were similar to those probably obtained by cigarette smokers, but the different routes and rates of administration make precise comparisons difficult. However, it is suggested that relapse to tobacco use in man may be associated with the persistence of tolerance.
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