Does nicotine affect D2 receptor upregulation? A case-control study

  • Silvestri S
  • Negrete J
  • Seeman M
 et al. 
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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 [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.

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.

Author-supplied keywords

  • D2 receptor upregulation
  • Human PET study
  • Nicotine

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  • S. Silvestri

  • J. C. Negrete

  • M. V. Seeman

  • C. M. Shammi

  • P. Seeman

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