The hypothesis for this research was that regional cerebral blood flow (rCB
F) would increase following nasal nicotine administration to overnight abst
inent tobacco smokers in relationship to the known brain distribution of ni
cotinic cholinergic receptors (nAChRs). Nine male and nine female healthy a
dult smokers were studied. They abstained overnight from tobacco products f
or 10 or more hours prior to study the next morning. Nicotine nasal spray w
as given in doses of 1-2.5 mg total with half in each nostril while the sub
ject was awake and resting in a supine position. Oleoresin of pepper soluti
on in a similar volume was used as an active placebo to control for the irr
itating effects of nicotine. Both substances were given single blind to the
subjects. Positron emission tomography (PET) with (H2O)-O-15 was used to m
easure 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, cons
istent with the irritant effects of both substances. The mean rCBF effects
of nasal pepper were subtracted from those of nasal nicotine to determine t
he actions of nicotine alone. The latter produced increases in rCBF in the
thalamus, pens, Brodman area 17 of the visual cortex, and cerebellum. Some
brain areas that contain a large number of nAChRs, such as the thalamus, sh
owed an increase in CBF. Other areas that have few nAChRs, such as the cere
bellum, also showed an increase in relative CBF. The hippocampal/parahippoc
ampal 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 secondar
y effects of nicotine in which only some regional brain CBF changes correla
te with the known distribution of nAChR. No gender differences were noted.
(C) 2000 Wiley-Liss, Inc.