| Title | Toward brain imaging of serotonin 5-HT1A autoreceptor internalization. | | Author(s) | Zimmer L, Riad M, Rbah L, Belkacem-Kahlouli A, Le Bars D, Renaud B, Descarries L | | Institution | Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, Université Claude Bernard, Lyon, France. zimmer@cermep.fr | | Source | Neuroimage 2004 Jul; 22(3):1421-6. | | MeSH | 8-Hydroxy-2-(di-n-propylamino)tetralin
Animals
Autoradiography
Autoreceptors
Binding Sites
Brain
Cell Membrane
Cytoplasm
Extracellular Fluid
Kinetics
Ligands
Male
Microdialysis
Microscopy, Immunoelectron
Osmolar Concentration
Piperazines
Pyridines
Raphe Nuclei
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A
Research Support, Non-U.S. Gov't
Serotonin Agonists
Serotonin Antagonists
Subcellular Fractions
Tissue Distribution
| | Abstract | Enhancing cerebral serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is a common property of antidepressant treatments and the basis for their efficacy. 5-HT1A receptors located on the cell body and dendrites of 5-HT neurons (autoreceptors) play a key role in this regard. Because they normally mediate an inhibition of neuronal firing, their desensitization is a prerequisite to the delayed enhancement of 5-HT neurotransmission upon treatment with monoamine oxidase (MAOI) inhibitors or specific serotonin reuptake inhibitors (SSRI). Using beta-sensitive microprobes in vivo, we measured a significant decrease (-30%) in binding sites for the 5-HT1A PET radioligand [18F]MPPF associated with an equivalent reduction (-34%) in the cell surface density of 5-HT1A receptor immunoreactivity (internalization), in the nucleus raphe dorsalis (autoreceptors), but not hippocampus (heteroreceptors), of rats given a single dose of the specific 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, iv). This effect was completely blocked by pretreatment with the selective 5-HT1A antagonist WAY 100635. Having ruled out that this decreased density of [18F]MPPF binding in the nucleus raphe dorsalis of 8-OH-DPAT-treated rats resulted from a local blood flow effect, we obtained autoradiographic evidence indicating that the total amount of specific binding of [18F]MPPF in tissue sections was unaffected by the 8-OH-DPAT treatment in either NRD or hippocampus. It was therefore concluded that the internalization of 5-HT1A autoreceptors accounted for the decreased binding in vivo of [18F]MPPF in the nucleus raphe dorsalis of rats treated with 8-OH-DPAT. Thus, PET imaging might provide a mean to measure 5-HT1A receptor internalization in human brain and thus assess responsiveness to antidepressant treatment. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15219613 |
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