Smoking produces rapid rise of [11C]nicotine in human brain.
BACKGROUND
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 [(11)C]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.
Berridge
Marc S
MS
3D Imaging LLC, Cyclotron Suite Rm PS010, UAMS Radiology #556, 4301 W. Markham St., Little Rock, AR, 72205-7199, USA. MBerridge@3DImagingLLC.com
Apana
Scott M
SM
Nagano
Kenichi K
KK
Berridge
Catherine E
CE
Leisure
Gregory P
GP
Boswell
Mark V
MV
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000378:metabolism*; D055815:Young Adult
D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; D009538:Nicotine