Association of low striatal dopamine D2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse

Objective: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D-2) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy- smoking nicotine-dependent smokers. Method: In vivo D-2/D-3 receptor availability was determined with [F-18] fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation. Results: Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D-2/D-3 receptors within the bilateral putamen functionally covering parts of the dorsal striatum, as compared to the never-smoking subjects. Nicotine craving under the consumption condition correlated positively with D-2/D-3 receptor availability within the ventral striatum but negatively with D-2/D-3 receptor availability within the anterior cingulate and inferior temporal cortex. Conclusions: Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D-2/D-3 receptors. In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D-2/D-3 receptor availabilities, with higher availability within the ventral striatum but lower availability within the anterior cingulate and inferior temporal cortex.