Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain.
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.
Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
Emma Jane
EJ
Rose
Thomas J
TJ
Ross
Betty Jo
BJ
Salmeron
Mary
M
Lee
Diaa M
DM
Shakleya
Marilyn
M
Huestis
Elliot A
EA
Stein
D000328:Adult; D016022:Case-Control Studies; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D003463:Cues; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012201:Reward; D013997:Time Factors; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000097:blood / Q000503:physiopathology*
D009538:Nicotine