A PET imaging study of 5-HT sub(1A) receptors in cat brain after acute and chronic fluoxetine treatment

• Published in: NeuroImage (Orlando, Fla.) Vol. 33; no. 3; pp. 834 - 842
• Main Authors: Aznavour, Nicolas, Rbah, Latifa, Riad, Mustapha, Reilhac, Anthonin, Costes, Nicolas, Descarries, Laurent, Zimmer, Luc
• Format: Journal Article
• Language: English
• Published: 01.11.2006
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2006.08.012

Immuno-electron microscopic and beta -microprobe studies have demonstrated that the internalization of serotonin 5-HT sub(1A) autoreceptors, after acute treatment with the selective 5-HT sub(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 [ super(18)F]MPPF in the nucleus raphe dorsalis (NRD) of rat. To determine whether this event might be amenable to brain imaging, the present [ super(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, [ super(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, [ super(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 sub(1A) autoreceptors on the plasma membrane of NRD dendrites was comparable to control after chronic fluoxetine treatment. If the decrease in [ super(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.