Nornicotine is self-administered intravenously by rats

• Published in: Psychopharmacologia Vol. 146; no. 3; pp. 290 - 296
• Main Authors: BARDO, M. T, GREEN, T. A, CROOKS, P. A, DWOSKIN, L. P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.10.1999; Springer Nature B.V
• Subjects: Alkaloids; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Drug dependence; Drug self-administration; Male; Medical sciences; Nicotine; Nicotine - administration & dosage; Nicotine - analogs & derivatives; Nornicotine; Operant conditioning; Rats; Rats, Sprague-Dawley; Reinforcement (Psychology); Self Administration; Stereoisomerism; Tobacco; Tobacco smoking; Tobacco, tobacco smoking; Toxicology; Intravenous administration; Rat; Rodentia; Tobacco smoking; Instrumental conditioning; Self administration; Dose activity relation; Learning; Vertebrata; Mammalia; Acquisition process; Animal; Dependence; Reinforcement; Behavior; Stimulus discrimination; Chemical stimulus; Nicotine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130051119

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.