Nicotine-induced limbic cortical activation in the human brain: a functional MRI study.
OBJECTIVE
Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates.


METHODS
Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials.


RESULTS
Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans.


CONCLUSIONS
The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.
Department of Psychiatry, Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA. estein@mcw.edu
E A
EA
Stein
J
J
Pankiewicz
H H
HH
Harsch
J K
JK
Cho
S A
SA
Fuller
R G
RG
Hoffmann
M
M
Hawkins
S M
SM
Rao
P A
PA
Bandettini
A S
AS
Bloom
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012054:Reinforcement, Psychology; D016540:Smoking Cessation; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000628:therapy
D011978:Receptors, Nicotinic; D009538:Nicotine