Pharmacokinetics of nicotine in adult and infant mice

Experiments were done to compare the time-courses of the nicotine concentration in the blood, heart, and brain of infant and adult mice after small and large single doses of radioactive nicotine tartrate. In some experiments the nicotine receptors were blocked with mecamylamine or hexamethonium, and their effects on nicotine levels were measured. The nicotine-induced tremor was allowed visually, and its effects on the heart rate were measured by ECG. In adult mice the peak levels of brain nicotine occurred at 10 min, whereas in infant mice the brain nicotine levels were still rising at 20 min. In the latter the blood and heart nicotine levels were higher than the respective brain levels, and the nicotine level in the brain stem exceeded the hemisphere level. The results were reversed in adult mice. A remarkable accumulation of nicotine in the infant heart was measured. Pretreatment with mecamylamine lowered brain nicotine levels in adult mice, and in infant mice the nicotine levels in blood and heart were lowered as well. This pretreatment abolished the nicotine tremor and its effects on the heart rate similarly in both age groups. This suggests that the difference in nicotine levels after mecamylamine in infant and adult mice may not depend solely on possible differences in circulatory changes but can represent differences in "receptor population" as well. Hexamethonium did not abolish the central depressant effect of nicotine on the heart rate nor did it lower the brain nicotine levels. This supports the view that there is some correlation of the central effects of nicotine and its brain levels.