Nicotine-induced dopamine release in primates measured with [11C]raclopride PET.
Nicotine-induced dopamine (DA) release constitutes a pharmacological probe of the DA system that has potential use in patients with schizophrenia, who have abnormally elevated DA release after amphetamine administration and possibly abnormalities in nicotinic signaling. We performed positron emission tomography studies in five rhesus monkeys that received i.v. nicotine doses ranging from 0.01 to 0.06 mg/kg. [(11)C]raclopride was administered with either a bolus plus constant infusion or with paired bolus injections. The dynamics of D-2-binding potential (BP) after nicotine administration were studied and compared to amphetamine. Nicotine caused a significant albeit small reduction (5%, p<0.03) in BP, regardless of methodology of tracer administration. This effect disappeared 2.5 h after nicotine administration. Amphetamine caused much larger and prolonged displacement of [(11)C]raclopride as compared to nicotine. There was no correlation between changes in BP and nicotine dose or plasma level. Regional differences in the nicotine effect within the basal ganglia were not found. Our data are consistent with the increase in DA detected with microdialysis in animals after acute nicotine administration, however, a larger effect size would be desirable to attempt studies comparing human smokers with and without schizophrenia.
Marenco
Stefano
S
Clinical Brain Disorders Branch, IRP, NIMH, USA. marencos@intra.nimh.nih.gov
Carson
Richard E
RE
Berman
Karen Faith
KF
Herscovitch
Peter
P
Weinberger
Daniel R
DR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020891:Raclopride / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods*
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D020891:Raclopride; D009538:Nicotine; D000661:Amphetamine; D004298:Dopamine