Does nicotine affect D2 receptor upregulation? A case-control study.
OBJECTIVE
Nicotine has a powerful preventive effect on neuroleptic-induced dopamine D2 receptor upregulation in the rat. The aim of this human positron emission tomography (PET) study was to compare upregulation in a smoker and a non-smoker, both of whom had received haloperidol for the same duration of time.


METHODS
Two subjects who had been treated for 16 years with a constant dose of haloperidol were scanned after temporary haloperidol withdrawal, using [11C]-raclopride.


RESULTS
The non-smoker, who had received a dose of 10 mg/day, showed a D2 upregulation of 98% and developed severe and persistent symptoms of tardive dyskinesia (TD) upon withdrawal. The chronic smoker, who had been treated with 40 mg/day, displayed a D2 upregulation of 71% and did not develop TD.


CONCLUSIONS
These human observations agree with animal data which showed that nicotine can decrease neuroleptic-induced D2 receptor upregulation. This property of nicotine may play a protective role in movement disorders whose pathophysiology involves D2 receptor hypersensitivity.
Silvestri
S
S
Centre for Addictions and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Negrete
J C
JC
Seeman
M V
MV
Shammi
C M
CM
Seeman
P
P
D000328:Adult; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D012907:Smoking; D014055:Tomography, Emission-Computed; D015854:Up-Regulation / Q000187:drug effects*
D017448:Receptors, Dopamine D2; D009538:Nicotine