QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.085381v1 314/2/636    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lockman, P. R. Articles by Allen, D. D. Search for Related Content PubMed PubMed Citation Articles by Lockman, P. R. Articles by Allen, D. D.

NEUROPHARMACOLOGY

Brain Uptake Kinetics of Nicotine and Cotinine after Chronic Nicotine Exposure

Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas

Blood-brain barrier (BBB) nicotine transfer has been well documented 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 morphology. 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 distribution 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 in situ brain perfusion model, we assessed the BBB uptake of [³H]nicotine and [³H]cotinine in naive animals and in animals exposed chronically to S-(–)nicotine (4.5 mg/kg/day) through osmotic minipump infusion. Our data demonstrate that 1) [³H]nicotine BBB uptake is not altered in the in situ perfusion model after chronic nicotine exposure, 2) [³H]cotinine penetrates the BBB, and 3) similar to [³H]nicotine, [³H]cotinine BBB transfer is not altered by chronic nicotine exposure. To our knowledge, this is the first report detailing the uptake of nicotine and cotinine after chronic nicotine exposure and quantifying the rate of BBB penetration by cotinine.

Address correspondence to: Dr. Paul R. Lockman, Department of Pharmaceutical Sciences, Texas Tech University HSC, 1300 So. Coulter Dr., Amarillo, TX 79106-1712. E-mail: paul.lockman{at}ttuhsc.edu

This article has been cited by other articles:

				P. R. Lockman, V. K. Manda, W. J. Geldenhuys, R. K. Mittapalli, F. Thomas, Z. F. Albayati, P. A. Crooks, L. P. Dwoskin, and D. D. Allen Carrier-Mediated Transport of the Quaternary Ammonium Neuronal Nicotinic Receptor Antagonist N,N'-Dodecylbispicolinium Dibromide at the Blood-Brain Barrier J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 244 - 250. [Abstract] [Full Text] [PDF]

				E. C. K. Siu and R. F. Tyndale Characterization and Comparison of Nicotine and Cotinine Metabolism in Vitro and in Vivo in DBA/2 and C57BL/6 Mice Mol. Pharmacol., March 1, 2007; 71(3): 826 - 834. [Abstract] [Full Text] [PDF]