PET Studies of the Influences of Nicotine on Neural Systems in Cigarette Smokers

• Published in: The American journal of psychiatry Vol. 160; no. 2; pp. 323 - 333
• Main Authors: Rose, Jed E., Behm, Frederique M., Westman, Eric C., Mathew, Roy J., London, Edythe D., Hawk, Thomas C., Turkington, Timothy G., Coleman, R. Edward
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.02.2003; American Psychiatric Association
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Amygdala - blood supply; Amygdala - diagnostic imaging; Amygdala - drug effects; Arousal - drug effects; Arousal - physiology; Biological and medical sciences; Blood flow; Brain; Brain - blood supply; Brain - diagnostic imaging; Brain - drug effects; Brain activity; Female; Humans; Male; Medical sciences; Middle Aged; Nicotine; Nicotine - adverse effects; Nicotine - pharmacology; Oxygen Radioisotopes; Positron emission tomography; Psychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Reward; Smokers; Smoking; Smoking - adverse effects; Smoking - physiopathology; Smoking cessation; Tobacco smoking; Tomography, Emission-Computed - statistics & numerical data; Water; Withdrawal symptoms; Radionuclide study; Frontal lobe; Intravenous administration; Amygdala; Craving; Central nervous system; Dose activity relation; Mecamylamine; Cigarette; Alkaloid; Motivation; Antagonist; Biological effect; Laterality; Withdrawal syndrome; Nicotinic receptor; Consumption; Human; Regional blood flow; Hemispheric specialization; Reticuloendothelial system; Healthy subject; Attitude; Corpus striatum; Symptomatology; Ganglioplegic; Hemodynamics; Comparative study; Brain (vertebrata); Nicotine; Positron; Emission tomography
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.160.2.323

OBJECTIVE: The effects of acute nicotine administration and smoking on brain function were investigated in two studies, with the primary goal of identifying neural systems that mediate these effects. METHOD: In study 1, 18 healthy volunteer cigarette smokers were exposed to three conditions in a single session: 1) smoking a nicotine-containing cigarette, 2) smoking a denicotinized cigarette, or 3) receiving intravenous nicotine injections in conjunction with smoking a denicotinized cigarette. In study 2, 16 subjects smoked a nicotine-containing and denicotinized cigarette in each of two sessions 2 hours after receiving the nicotinic antagonist mecamylamine (10 mg) or placebo orally. Regional cerebral blood flow (rCBF) was assessed by using the bolus 15O-labeled water method and positron emission tomography. Subjective measures of smoking withdrawal symptoms were also collected. RESULTS: A principal-components analysis of rCBF data pooled from the two studies identified three factors consisting of frontal, striatal, and reticular systems. The amygdala was considered as a separate region of interest. Nicotine increased normalized rCBF in the left frontal region and decreased rCBF in the left amygdala. The rCBF in the right hemisphere reticular system was related to nicotine dose in an inverted-U-shaped pattern and was strongly related to self-reported craving for cigarettes and to the addiction scale of a smoking motivation questionnaire. The effects of mecamylamine on rCBF were generally opposite to those of nicotine. CONCLUSIONS: The results indicate that nicotine influences brain regions involved in arousal and reward and suggest specific functional systems that may be linked to motivationally significant aspects of tobacco dependence.