DISCRIMINATIVE STIMULUS EFFECTS OF NICOTINE AND CHRONIC TOLERANCE

Tolerance to discriminative stimulus (DS) effects of drugs, as observe d by a shift of the dose-response curve to the right, has been observe d with many addictive drugs (e.g. amphetamine, cocaine and morphine). Chronic administration of nicotine has been reported to produce tolera nce to the locomotor depressant effects and aversive stimulus properti es of nicotine; however, the DS effects of nicotine have not been exam ined for development of tolerance following chronic treatment. We repo rt on experiments utilising a cumulative-dosing drug discrimination pa radigm. Eight, male Sprague-Dawley rats were trained to discriminate n icotine (0.4 mg/kg s.c.) from saline under a fixed ratio (FR 10) sched ule for food reinforcement. Multiple training sessions were given dail y, and once criteria was met, cumulative doses of nicotine (0.025-1.2 mg/kg s.c.) were evaluated. Rats acquired the nicotine discrimination after 80 sessions. During this period, rats developed tolerance to the rate-depressing effects of nicotine after 20 nicotine-training sessio ns. Chronic treatments of nicotine in the rat's home cage for 7 days d uring suspended training failed to shift the dose-response curve for n icotine. Increasing the frequency to three daily injections also had n o effect on nicotine discrimination. Furthermore, continuous infusions of nicotine (6.4 mg/kg/day) delivered via osmotic minipumps failed to shift the dose-response curve. No physical signs of withdrawal were a pparent, particularly on lever responding, following removal of the mi nipump. These results suggest that under the conditions described, chr onic tolerance to nicotine's DS does not develop readily. Copyright (C ) 1997 Elsevier Science Inc.