The effect of nicotine on striatal dopamine release in man: A [11C]raclopride PET study.
In common with many addictive substances and behaviors nicotine activates the mesolimbic dopaminergic system. Brain microdialysis studies in rodents have consistently shown increases in extrasynaptic DA levels in the striatum after administration of nicotine but PET experiments in primates have given contradicting results. A recent PET study assessing the effect of smoking in humans showed no change in [(11)C]raclopride binding in the brain, but did find that "hedonia" correlated with a reduction in [(11)C]raclopride binding suggesting that DA may mediate the positive reinforcing effects of nicotine. In this experiment we measured the effect of nicotine, administered via a nasal spray, on DA release using [(11)C]raclopride PET, in 10 regular smokers. There was no overall change in [(11)C]raclopride binding after nicotine administration in any of the striatal regions examined. However, the individual change in [(11)C]raclopride binding correlated with change in subjective measures of "amused" and "happiness" in the associative striatum (AST) and sensorimotor striatum (SMST). Nicotine concentration correlated negatively with change in BP in the limbic striatum. Nicotine had significant effects on cardiovascular measures including pulse rate, systolic blood pressure (BPr), and diastolic BPr. Baseline [(11)C]raclopride binding potential (BP) in the AST correlated negatively with the Fagerström score, an index of nicotine dependence. These results support a role for the DA system in nicotine addiction, but reveal a more complex relationship than suggested by studies in animals.
Montgomery
Andrew J
AJ
MRC-Clinical Sciences Centre, Imperial College, Hammersmith Hospital, London W12 0NN, United Kingdom. andrew.montgomery@ic.ac.uk
Lingford-Hughes
Anne R
AR
Egerton
Alice
A
Nutt
David J
DJ
Grasby
Paul M
PM
D000328:Adult; D000339:Affect / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D020891:Raclopride
D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D020891:Raclopride; D009538:Nicotine; D004298:Dopamine