The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11C]FLB 457 in healthy subjects

Eur J Nucl Med Mol Imaging. 2009 Mar;36(3):475-83. doi: 10.1007/s00259-008-0969-9. Epub 2008 Nov 5.

Abstract

Purpose: The dopamine D(2)/D(3) receptor ligand [(11)C]FLB 457 and PET enable quantification of low-density extrastriatal D(2)/D(3) receptors, but it is uncertain whether [(11)C]FLB 457 can be used for measuring extrastriatal dopamine release.

Methods: We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [(11)C]FLB 457 binding potential (BP(ND)) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers.

Results: The effects of d-amphetamine on [(11)C]FLB 457 BP(ND) and distribution volume (V(T)) in the frontal cortex were not different from those of placebo. Small decreases in [(11)C]FLB 457 BP(ND) were observed only in the posterior cingulate and hippocampus. The regional changes in [(11)C]FLB 457 BP(ND) did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria.

Conclusion: This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D(2)/D(3) receptor binding. Our results indicate that [(11)C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging*
  • Brain / drug effects*
  • Brain / metabolism
  • Carbon Radioisotopes*
  • Dextroamphetamine / pharmacology*
  • Dopamine / metabolism
  • Double-Blind Method
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Male
  • Positron-Emission Tomography
  • Pyrrolidines*
  • Radiopharmaceuticals*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Salicylamides*
  • Young Adult

Substances

  • Carbon Radioisotopes
  • Pyrrolidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Salicylamides
  • FLB 457
  • Dextroamphetamine
  • Dopamine