Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers.

Several drugs of abuse, including nicotine, are thought to exert their reinforcing effects through actions on the mesolimbic dopamine system. Animal and human studies suggest that chronic administration of addictive drugs may lead to impaired dopamine neurotransmission in the nucleus accumbens. We measured D1 receptor density in 11 smokers and 18 nonsmokers using positron emission tomography and the D1 receptor ligand [11C]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 control subjects were scanned twice to assess the reproducibility of the method. We used compartmental modeling to measure [11C]SCH 23390 binding potential, a measure of D1 receptor density. There were no differences in binding between abstinent and nonabstinent scans in smokers or in the two scans in controls. However, there was a significant reduction in [11C]SCH 23390 binding potential in smokers compared to nonsmokers in the striatum, most prominently 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 mesolimbic dopamine system may be chronically underactive in smokers, either as an antecedent or consequence of addiction to cigarettes. Such a hypodopaminergic state may play an important role in sustaining nicotine-seeking behavior. Alternatively, an inherited reduction in dopamine receptors in the striatum may be associated with an increased risk of addictive behavior.