Nornicotine is self-administered intravenously by rats

Rationale: Nicotine is a tobacco alkaloid known to be important in the acqu isition and maintenance of tobacco smoking. However, other constituents in tobacco may contribute to the dependence liability. Objective: The present report sought to determine whether nornicotine, a tobacco alkaloid and meta bolite of nicotine, has a reinforcing effect. Methods: Rats were prepared w ith a jugular catheter, then were allowed to self-administer intravenously either S(-)-nicotine (0.03 mg/kg/infusion), RS(+/-)-nornicotine (0.3 mg/kg/ infusion) or saline using a two-lever operant procedure. The response requi rement for each infusion was incremented gradually from a fixed ratio 1 (FR 1) to FR5. When responding stabilized on the FR5, other doses of nicotine ( 0.01 mg/kg/infusion and 0.06 mg/kg/infusion) and nornicotine (0.075, 0.15, and 0.6 mg/kg/infusion) were tested for their ability to control responding . Results: Similar to nicotine, rats self-administered nornicotine signific antly above saline control levels. Within the dose ranges tested, both nico tine and nornicotine yielded relatively flat dose-response functions. Extin ction of responding was evident when saline was substituted for nornicotine , and responding was reinstated when nornicotine again was available. The r ate of nornicotine self-administration was similar between rats tested with either 24-h or 48-h inter-session intervals. Conclusion: These results ind icate that nornicotine contributes to the dependence liability associated w ith tobacco use.