title: Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers.
abstract: The hypothesis for this research was that regional cerebral blood flow (rCBF) would increase following nasal nicotine administration to overnight abstinent tobacco smokers in relationship to the known brain distribution of nicotinic cholinergic receptors (nAChRs). Nine male and nine female healthy adult smokers were studied. They abstained overnight from tobacco products for 10 or more hours prior to study the next morning. Nicotine nasal spray was given in doses of 1-2.5 mg total with half in each nostril while the subject was awake and resting in a supine position. Oleoresin of pepper solution in a similar volume was used as an active placebo to control for the irritating effects of nicotine. Both substances were given single blind to the subjects. Positron emission tomography (PET) with H(2)(15)O was used to measure rCBF. The data from each subject volunteer were normalized to global activity to better assess regional brain changes. Both nasal nicotine and pepper spray produced similar increases in CBF in somesthetic area II, consistent with the irritant effects of both substances. The mean rCBF effects of nasal pepper were subtracted from those of nasal nicotine to determine the actions of nicotine alone. The latter produced increases in rCBF in the thalamus, pons, Brodman area 17 of the visual cortex, and cerebellum. Some brain areas that contain a large number of nAChRs, such as the thalamus, showed an increase in CBF. Other areas that have few nAChRs, such as the cerebellum, also showed an increase in relative CBF. The hippocampal/parahippocampal areas showed greater regional decreases (left) and lesser increases (right) in CBF that correlated with the increase in plasma arterial nicotine concentrations. The results obtained indicate complex primary and secondary effects of nicotine in which only some regional brain CBF changes correlate with the known distribution of nAChR. No gender differences were noted.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Domino
authors.forename: S
authors.initials: S
authors.lastname: Minoshima
authors.forename: S
authors.initials: S
authors.lastname: Guthrie
authors.forename: L
authors.initials: L
authors.lastname: Ohl
authors.forename: L
authors.initials: L
authors.lastname: Ni
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: J K
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000097:blood / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012146:Rest / Q000502:physiology; D016037:Single-Blind Method; D012907:Smoking / Q000097:blood; D014055:Tomography, Emission-Computed
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D002211:Capsaicin