Decreased [18F]MPPF binding potential in the dorsal raphe nucleus after a single oral dose of fluoxetine: a positron-emission tomography study in healthy volunteers

Biol Psychiatry. 2008 Jun 15;63(12):1135-40. doi: 10.1016/j.biopsych.2007.11.016. Epub 2008 Jan 14.


Background: Brain serotonin-1A (5-HT(1A)) autoreceptors internalize when activated by agonist or by their endogenous ligand, serotonin. This positron-emission tomography (PET) study tested the hypothesis that 5-HT(1A) autoreceptor internalization might be indexed in vivo by a decrease in the specific binding of the 5-HT(1A) radioligand, 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide ([(18)F]MPPF), in the dorsal raphe nucleus (DRN) of healthy adult men administered a single oral dose of the selective serotonin reuptake inhibitor, fluoxetine.

Methods: [(18)F]MPPF binding potential was measured in the DRN and other brain regions endowed with 5-HT(1A) receptors in eight healthy volunteers, 5 hours after the randomized, double-blind administration of fluoxetine (20 mg) or placebo.

Results: In every subject, [(18)F]MPPF binding potential was decreased in the DRN only (44% +/- 22 SD), in response to fluoxetine.

Conclusions: Imaging the functional state of 5-HT(1A) autoreceptors (i.e., internalization) in the human brain, using [(18)F]MPPF/PET, may represent a promising avenue for investigating the neurobiology of serotonin-related disorders and notably of major depression.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Autoreceptors / drug effects
  • Autoreceptors / metabolism
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Double-Blind Method
  • Fluorine Radioisotopes / pharmacokinetics*
  • Fluoxetine / pharmacology*
  • Humans
  • Image Processing, Computer-Assisted*
  • Magnetic Resonance Imaging*
  • Male
  • Piperazines
  • Positron-Emission Tomography*
  • Pyridines
  • Raphe Nuclei / diagnostic imaging*
  • Raphe Nuclei / drug effects*
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Reference Values


  • Antidepressive Agents, Second-Generation
  • Autoreceptors
  • Fluorine Radioisotopes
  • Piperazines
  • Pyridines
  • Fluoxetine
  • Receptor, Serotonin, 5-HT1A
  • 4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine