Tolerance to the disruptive effects of arecoline on schedule-controlled behavior.

The roles of dispositional, physiological, and behavioral factors in the development of tolerance to the effects of arecoline on operant behavior were assessed. In Experiment I, rats were trained to press a lever on a variable-interval 15-s schedule for milk reinforcement. Dose-effect relationships were assessed prior to and during chronic arecoline (1.74 mg/kg/day) treatment. After 21 days of arecoline administration prior to each session, the dose-effect relationship for total number of responses did not shift. However, the dose-effect relationship for total number of reinforcers shifted to the right. In Experiment II, rats were trained to respond on a fixed-ratio 20 schedule for milk reinforcement. Dose-effect relationships were assessed prior to and during chronic arecoline (0.87 mg/kg/day) administration. One group of rats received daily injections of arecoline prior to the session and a second group received arecoline injections 30 min after the session. Daily administration of arecoline resulted in a greater shift to the right of the dose-effect relationship for the presession group than it did for the postsession group. These data demonstrate the importance of behavioral factors in the development of tolerance to arecoline.