Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain

Biol Psychiatry. 2012 Feb 1;71(3):206-13. doi: 10.1016/j.biopsych.2011.09.013. Epub 2011 Oct 26.


Background: The reinforcing effects of nicotine are mediated by brain regions that also support temporal difference error (TDE) processing; yet, the impact of nicotine on TDE is undetermined.

Methods: Dependent smokers (n = 21) and matched control subjects (n = 21) were trained to associate a juice reward with a visual cue in a classical conditioning paradigm. Subjects subsequently underwent functional magnetic resonance imaging sessions in which they were exposed to trials where they either received juice as temporally predicted or where the juice was withheld (negative TDE) and later received unexpectedly (positive TDE). Subjects were scanned in two sessions that were identical, except that smokers had a transdermal nicotine (21 mg) or placebo patch placed before scanning. Analysis focused on regions along the trajectory of mesocorticolimbic and nigrostriatal dopaminergic pathways.

Results: There was a reduction in TDE-related function in smokers in the striatum, which did not differ as a function of patch manipulation but was predicted by the duration (years) of smoking. Activation in midbrain regions was not impacted by group or drug condition.

Conclusions: These data suggest a differential effect of smoking status on the neural substrates of reward in distinct dopaminergic pathway regions, which may be partially attributable to chronic nicotine exposure. The failure of transdermal nicotine to alter reward-related functional processes, either within smokers or between smokers and control subjects, implies that acute nicotine patch administration is insufficient to modify reward processing, which has been linked to abstinence-induced anhedonia in smokers and may play a critical role in smoking relapse.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Case-Control Studies
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiology
  • Corpus Striatum / physiopathology
  • Cues
  • Female
  • Functional Neuroimaging / methods
  • Functional Neuroimaging / psychology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / psychology
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / physiology
  • Mesencephalon / physiopathology
  • Nicotine / administration & dosage
  • Nicotine / blood
  • Nicotine / pharmacology*
  • Reward*
  • Time Factors
  • Tobacco Use Cessation Devices
  • Tobacco Use Disorder / blood
  • Tobacco Use Disorder / physiopathology*


  • Nicotine