Brain uptake kinetics of nicotine and cotinine after chronic nicotine exposure

Blood-brain barrier (BBB) nicotine transfer has been well doc-umented in view of the fact that this alkaloid is a cerebral blood flow marker. However, limited data are available that describe BBB penetration of the major tobacco alkaloids after chronic nicotine exposure. This question needs to be addressed, given long-term nicotine exposure alters both BBB function and mor-phology. In contrast to nicotine, it has been reported that cotinine (the major nicotine metabolite) does not penetrate the BBB, yet cotinine brain distribution has been well documented after nicotine exposure. Surprisingly, therefore, the literature indirectly suggests that central nervous system cotinine distri-bution occurs secondarily to nicotine brain metabolism. The aims of the current report are to define BBB transfer of nicotine and cotinine in naive and nicotine-exposed animals. Using an i