Association of low striatal dopamine d2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse

Am J Psychiatry. 2008 Apr;165(4):507-14. doi: 10.1176/appi.ajp.2007.07020352. Epub 2008 Mar 3.


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 [ (18)F]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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basal Ganglia / chemistry
  • Basal Ganglia / diagnostic imaging*
  • Basal Ganglia / metabolism*
  • Behavior, Addictive / diagnosis
  • Behavior, Addictive / diagnostic imaging
  • Behavior, Addictive / metabolism*
  • Benzamides / metabolism
  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Functional Laterality / physiology*
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism
  • Humans
  • Male
  • Positron-Emission Tomography / statistics & numerical data*
  • Pyrrolidines / metabolism
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3
  • Smoking / adverse effects
  • Smoking / psychology
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / diagnostic imaging
  • Substance Withdrawal Syndrome / metabolism
  • Substance-Related Disorders / diagnosis
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / metabolism
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / metabolism
  • Tobacco Use Disorder / diagnosis
  • Tobacco Use Disorder / diagnostic imaging*
  • Tobacco Use Disorder / metabolism*


  • Benzamides
  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3