Abstract
Rationale
Variation in the rate at which drugs reach the brain influences many different drug effects and is also thought to influence liability to addiction. For example, rapid intravenous delivery of cocaine and nicotine is more effective in producing hedonic effects, tolerance, psychomotor sensitization, and in inducing gene expression. Smoking is thought to result in an especially rapid rate of rise of nicotine in the brain, but whether this is true has never been adequately addressed. Thus, in this study, we sought to determine the true rate of rise of smoked nicotine in human brain and compare this with previous intravenous nicotine delivery.
Methods
Positron emission tomography scans of lung and brain regions and arterial and venous blood curves were obtained in human subjects after single puffs from cigarettes formulated with [11C]nicotine.
Results
The rise of nicotine concentration following a single puff was rapid, reaching more than 50% of maximum brain levels within 15 s of bolus arrival in the brain in most subjects. This rate of rise was considerably faster than that seen in previous studies using intravenous administration.
Conclusions
Uptake in human brain from a single inhalation was sufficiently rapid that it is plausible that fast rate-of-rise contributes to nicotine dependence in smokers.
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Acknowledgments
We deeply appreciate the insight and assistance of Dr. Kent Berridge of the University of Michigan with data interpretation and for valuable comments and suggestions to improve the manuscript. We are also indebted to Dr. Terry Robinson of the University of Michigan for helpful critical reading of the manuscript and useful discussions. Constructive comments by the Editor and reviewers have also significantly contributed to the quality of this manuscript. We thank Dr. Joanna Fowler of Brookhaven National Laboratory for valuable discussions and encouragement. Apparatus design and construction and cyclotron operation by Mr. Ken Volker, and PET scanning assistance provided by Mr. Ron Rogan and Ms. Ellie Leedom are gratefully acknowledged. This work was supported by the Philip Morris External Research Program; Philip Morris USA, Inc., and performed at a previous address of 3D Imaging, in collaboration with Case Western Reserve University, Cleveland, OH, USA.
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Berridge, M.S., Apana, S.M., Nagano, K.K. et al. Smoking produces rapid rise of [11C]nicotine in human brain. Psychopharmacology 209, 383–394 (2010). https://doi.org/10.1007/s00213-010-1809-8
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DOI: https://doi.org/10.1007/s00213-010-1809-8