Plasma concentrations of nicotine in rats during tolerance and chronic exposure studies.

A convenient GC/MS method for the quantitation of nicotine is described. Brief and rapid tolerance to the hypertensive action of nicotine was observed during acute administration. Rats continuously exposed to (+)- or (-)-nicotine for 6 days showed significant dose-related suppression of water intake and body-weight decreases for the initial 4 days; then water consumption slowly returned to control levels, while body weight increased, but failed to reach control levels. During the withdrawal period, water consumption rose to levels significantly higher than that of the tartaric acid and water controls. Body weight during the withdrawal phase continued to increase but remained below those of control animals. Blood concentration of nicotine during acute tolerance was found to be 64.3 +/- 17.8 ng/ml whereas the saline controls showed levels of 0.67 +/- 0.67 ng/ml. Nicotine levels which were not detectable before the administration of nicotine, were elevated and constant during days 1 and 6 of the infusion period (320 +/- 80 ng/ml of plasma) and fell to below levels of detectability 24 hr after the termination of the infusion.