Several drugs of abuse, including nicotine, are thought to exert their rein
forcing effects through actions on the mesolimbic dopamine system. Animal a
nd human studies suggest that chronic administration of addictive drugs may
lead to impaired dopamine neurotransmission in the nucleus accumbens. We m
easured DI receptor density in 11 smokers and 18 nonsmokers using positron
emission tomography and the D1 receptor ligand [C-11]SCH 23390. Ten of the
smokers were scanned twice, once after overnight abstinence from cigarettes
, and once while smoking at their usual rate, to account for possible acute
effects of cigarette smoking on D1 receptor binding. In addition, eight co
ntrol subjects were scanned twice to assess the reproducibility of the meth
od. We used compartmental modeling to measure [C-11]SCH 23390 binding poten
tial, a measure of D1 receptor density. There were no differences in bindin
g between abstinent and nonabstinent scans in smokers or in the two scans i
n controls. However, there was a significant reduction in [C-11]SCH 23390 b
inding potential in smokers compared to nonsmokers in the striatum, most pr
ominently in the ventral striatum. This suggests that there is a reduction
in dopamine D1 receptor density in the ventral striatum of human cigarette
smokers relative to nonsmokers, which implies that the postsynaptic mesolim
bic dopamine system may be chronically underactive in smokers, either as an
antecedent or consequence of addiction to cigarettes. Such a hypodopaminer
gic state may play an important role in sustaining nicotine-seeking behavio
r. Alternatively, an inherited reduction in dopamine receptors in the stria
tum may be associated with an increased risk of addictive behavior. Synapse
42:48-53, 2001. (C) 2001 Wiley-Liss, Inc.