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.
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.
Sibon
Igor
I
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Benkelfat
Chawki
C
Gravel
Paul
P
Aznavour
Nicolas
N
Costes
Nicolas
N
Mzengeza
Shadrek
S
Booij
Linda
L
Baker
Glen
G
Soucy
Jean-Paul
JP
Zimmer
Luc
L
Descarries
Laurent
L
D000284:Administration, Oral; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D004311:Double-Blind Method; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D011903:Raphe Nuclei / Q000000981:diagnostic imaging* / Q000187:drug effects*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values
D018687:Antidepressive Agents, Second-Generation; D017660:Autoreceptors; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011725:Pyridines; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; C416325:4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine