Dependent smoking leads to a decrease in striatal dopamine D2 receptor availability similar to other drugs of abuse

Abstract

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Objectives: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consume impairs the natural function of the mesolimbic dopamine system as shown by a decrease in the availability of striatal dopamine 2 (D2) receptors among patients suffering from cocaine, heroine, amphetamine and alcohol dependence. However, it is unclear whether similar changes can also be observed among heavy smoking nicotine dependent smokers. Methods: In vivo D2/D3 receptor availability was determined with [18F]-fallypride positron-emission tomography among 17 heavy smoking nicotine dependent subjects as well as 22 age-matched never-smoking subjects. The smokers were scanned twice; once under consume and second after overnight withdrawal. PET Scans were performed after i.v. injection of 180 MBq [18F]-fallypride, with 180 min. dynamic acquisition (Siemens ECAT EXACT-Scanner, 3D mode). The images were normalized and binding potentials were calculated by means of the simplified reference tissue model at a voxel level. Nicotine craving was measured by QSU-Score (questionnaire for smoking urge) before and after the PET examination. Statistical comparision and correlation were done using SPM99. Results: Independent of the withdrawal status, the nicotine dependent smokers displayed a significant decreased availability of striatal D2/D3 receptors as compared to the never-smoking subjects (p<0.0001 uncorrected on voxel-level). Nicotine craving under the consume condition correlated positively with D2/D3 receptor availability within the striatum (p<0.001 corrected on cluster-level), but negatively with D2/D3 receptor availability within the anterior cingulate cortex and the inferior temporal cortex (p<0.001 corrected on cluster-level). Conclusions: Similar to other drugs of abuse, nicotine dependent smoking induces a decreased availability of striatal D2/D3 receptors. In contrast to previous findings on abstinent alcohol dependent patients, we found counter moving changes in the D2/D3 receptor availability within striatal and extrastriatal regions that were correlated with nicotine craving.