PLASMA NICOTINE AND COTININE CONCENTRATIONS IN MICE AFTER CHRONIC ORAL NICOTINE ADMINISTRATION AND CHALLENGE DOSES

The relevance of oral nicotine administration to long-term nicotine tr eatment was investigated. Mice received nicotine in drinking water as the sole fluid for 7 weeks, the nicotine concentration being increased gradually from 50 to 500 mug/ml so that the maximum estimated daily d ose of nicotine was 60-65 mg/kg. The fluid intake started to decrease but weight gain did not alter during the first 3 weeks. At 7 weeks the mice drank 47% less and weighed 9% less than the controls. During the 24-h withdrawal, the fluid intake increased above that of the control s and the difference in body weights disappeared. After 7 weeks, the p lasma nicotine and cotinine concentrations were about similar to conce ntrations attained at 1 h after a subcutaneous nicotine dose of 3 mg/k g, and did not differ significantly from those at 2 and 4 weeks. After acute nicotine, the plasma cotinine concentrations rose more slowly a nd fell more quickly in 12-week-old mice than in 5-week-old mice. Howe ver, the chronic oral administration of nicotine for 7 weeks did not a lter the rate of nicotine elimination. Our results indicate that nicot ine can be administered to mice chronically and orally through drinkin g water in doses high enough to induce pharmacologically relevant plas ma nicotine concentrations.