A PET imaging study of 5-HT(1A) receptors in cat brain after acute and chronic fluoxetine treatment.
Immuno-electron microscopic and beta-microprobe studies have demonstrated that the internalization of serotonin 5-HT(1A) autoreceptors, after acute treatment with the selective 5-HT(1A) receptor agonist 8-OH-DPAT or with the specific serotonin reuptake inhibitor (SSRI) fluoxetine, is associated with a marked decrease in the in vivo binding of [(18)F]MPPF in the nucleus raphe dorsalis (NRD) of rat. To determine whether this event might be amenable to brain imaging, the present [(18)F]MPPF positron emission tomographic (PET) study was carried out in anesthetized cats given or not a single dose (5 mg/kg, i.v.) or chronically treated with fluoxetine (5 mg/kg, s.c. for 21 days). Compared to control, [(18)F]MPPF binding potential was considerably (and visibly) decreased in the cat NRD after acute fluoxetine treatment, while it remained unchanged in other brain regions. Unexpectedly, after chronic fluoxetine treatment, [(18)F]MPPF binding potential was not affected in any brain region. In parallel immuno-electron microscopic experiments carried out in rat, the density of 5-HT(1A) autoreceptors on the plasma membrane of NRD dendrites was comparable to control after chronic fluoxetine treatment. If the decrease in [(18)F]MPPF binding at the onset of SSRI treatment was detectable by PET imaging, it could potentially serve as a biological index of efficacy.
Aznavour
Nicolas
N
Laboratoire de Neuropharmacologie, Faculté de Pharmacie, Université Lyon 1, Lyon, France.
Rbah
Latifa
L
Riad
Mustapha
M
Reilhac
Anthonin
A
Costes
Nicolas
N
Descarries
Laurent
L
Zimmer
Luc
L
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000187:drug effects; D002415:Cats; D005473:Fluoxetine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008854:Microscopy, Electron; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D013997:Time Factors
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; C416325:4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine