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. Method:  Two subjects who had been treated for 16 years with a constant dose of haloperidol were scanned after temporary haloperidol withdrawal, using [ 11 C]‐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. Conclusion:  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.