Plasma nicotine and cotinine concentrations in mice after chronic oral nicotine administration and challenge doses

Abstract

The relevance of oral nicotine administration to long-term nicotine treatment 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 μg/ml so that the maximum estimated daily dose 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 controls and the difference in body weights disappeared. After 7 weeks, the plasma nicotine and cotinine concentrations were about similar to concentrations attained at 1 h after a subcutaneous nicotine dose of 3 mg/kg, and did not differ significantly from those at 2 and 4 weeks. After acute nicotine, the plasma cotinine concentrations rose more slowly and fell more quickly in 12-week-old mice than in 5-week-old-mice. However, the chronic oral administration of nicotine for 7 weeks did not alter the rate of nicotine elimination. Our results indicate that nicotine can be administered to mice chronically and orally through drinking water in doses high enough to induce pharmacologically relevant plasma nicotine concentrations.