The development of pharmacological tolerance to the effect of nicotine on schedule-controlled responding in mice.

The effects of nicotine in mice responding on a fixed-ratio schedule for a sweetened milk reinforcer were determined before, during and after daily administration of the drug. During chronic treatment, responding was initially depressed in a group of mice given presession injections of nicotine and gradually returned to prechronic baseline levels. Responding to single doses of nicotine shifted to the right following chronic treatment for animals receiving either presession or postsession chronic injections of 1.2 mg/kg nicotine. Following termination of chronic treatment, both groups lost tolerance to the chronic dose at similar rates. These data indicate that animals given chronic pre- and postsession injections of nicotine develop tolerance to the pharmacological effects of the drug and that behavioral variables do not influence the development of tolerance to nicotine.