Nicotine tolerance in rats; role of dose and dose interval.

In experimentally naive rats, nicotine reduced spontaneous locomotor activity in a dose-related manner. After a single pretreatment with nicotine, acute tolerance developed; this was shown by a shift of the dose-response curve, such that the dose of nicotine required to produce a given decrement in activity was multiplied by a factor of about 2.4. In a second experiment, a range of doses of nicotine was found to induce tolerance, but the dose inducing the maximum degree of tolerance was rather critical. The results demonstrated the importance of using a range of pretreatment and challenge doses when assessing tolerance to nicotine. However, frequently repeated doses were not necessary, since tolerance developed when nicotine was administered to rats only once in every 3 days. In terms of tolerance liability in rats, it seems that nicotine is not discriminable from other drugs upon which dependence can be established. [ABSTRACT FROM AUTHOR]