Nicotine accumulation in the mouse brain is age-dependent and is quantitatively different in various segments

Abstract

Mice, varying from newborn to adult mice, were injected intraperitoneally with 1 mg/kg of 14C-nicotine. The nicotine concentration in blood and different segments of the brain (Cerebellum, Pons and Medulla oblongata, Midbrain, B. olfactory, Hypothalamus, Hippocampus and Cortex) was determined in newborn (0-day old); in 1-, 3-, 5-, 7-, 9-, 12- and 17-day old; and in adult (26-day old) mice. The nicotine concentration in the blood did not differ in mice aged 0–12 days, but the concentration thereafter decreased substantially until adult age. The decrease was associated with metabolism of nicotine as evidenced by cotinine formation, as well accumulation in different regions of the brain. Irrespective of the small continuous brain growth from day 1 until adult age, the age dependent nicotine uptake was dramatically increased in all segments of the brain between 9 and 12 days of age. However, the various brain regions showed differences in magnitude of growth and age-dependent changes in the distribution of nicotine. The relative nicotine concentration in Pons Med. obl. seems to be high in young mice until 9 days of age; thereafter, the concentration decreases in comparison to the other regions. Conversely, the relative concentration in the hippocampus and cortex rises from day 9 to 17 of age. The present results show that the ability of the brain to accumulate nicotine increases with age, reaching a peek at day 12 of age. Furthermore, this study for the first time shows that the age-dependent brain nicotine accumulation is quantitatively different in the various segments of the brain.