Nornicotine is self-administered intravenously by rats.

Nicotine is a tobacco alkaloid known to be important in the acquisition and maintenance of tobacco smoking. However, other constituents in tobacco may contribute to the dependence liability. The present report sought to determine whether nornicotine, a tobacco alkaloid and metabolite of nicotine, has a reinforcing effect. Rats were prepared with 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 requirement for each infusion was incremented gradually from a fixed ratio 1 (FR1) 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. Similar to nicotine, rats self-administered nornicotine significantly above saline control levels. Within the dose ranges tested, both nicotine and nornicotine yielded relatively flat dose-response functions. Extinction of responding was evident when saline was substituted for nornicotine, and responding was reinstated when nornicotine again was available. The rate of nornicotine self-administration was similar between rats tested with either 24-h or 48-h inter-session intervals. These results indicate that nornicotine contributes to the dependence liability associated with tobacco use.