Agonist-Induced Internalization of Serotonin-1A Receptors in the Dorsal Raphe Nucleus (Autoreceptors) But Not Hippocampus (Heteroreceptors)

• Published in: The Journal of neuroscience Vol. 21; no. 21; pp. 8378 - 8386
• Main Authors: Riad, Mustapha, Watkins, Kenneth C, Doucet, Edith, Hamon, Michel, Descarries, Laurent
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.11.2001; Society for Neuroscience
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - administration & dosage; Animals; Autoreceptors - drug effects; Autoreceptors - metabolism; Cell Compartmentation; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cytoplasm - metabolism; Cytoplasm - ultrastructure; Dendrites - drug effects; Dendrites - metabolism; Dendrites - ultrastructure; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - ultrastructure; Immunohistochemistry; Injections, Intravenous; Male; Microscopy, Electron; Piperazines - administration & dosage; Pyridines - administration & dosage; Raphe Nuclei - drug effects; Raphe Nuclei - metabolism; Raphe Nuclei - ultrastructure; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Receptors, Serotonin, 5-HT1; Serotonin Antagonists - administration & dosage; Serotonin Receptor Agonists - administration & dosage
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.21-21-08378.2001

Serotonin-1A (5-HT(1A)) receptors in the CNS are a major target for psychotropic drugs. In nucleus raphe dorsalis (NRD) and hippocampus (CA3), the selective 5-HT(1A) agonist (+)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) reduces the firing activity of serotoninergic (5-HT) and pyramidal neurons, respectively. When located on 5-HT (autoreceptors), but not on non-5-HT (heteroreceptors) neurons, 5-HT(1A) receptors are known to be subject to desensitization. Using quantitative electron microscopy after pre-embedding immunogold labeling with specific antibodies, we examined the subcellular distribution of these receptors after acute administration of 8-OH-DPAT (0.5 mg/kg, i.v.). Silver-intensified immunogold particles associated with the plasma membrane or the cytoplasm were counted in somata and dendrites within the NRD, 15 min, 1 hr and 24 hr after 8-OH-DPAT injection, and in hippocampal dendrites 1 hr after the same treatment. Significant decrease in the density of membrane labeling and concomitant increase of cytoplasmic labeling were demonstrated in the NRD, 15 min and 1 hr after 8-OH-DPAT administration, with a return to baseline level at 24 hr. Internalization was blocked by previous administration of the 5-HT(1A) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY 100635), which, by itself, was without apparent effect. In hippocampus (CA3), there were no apparent changes in the distribution of the receptor after 8-OH-DPAT administration. These findings are in line with earlier results showing a desensitization of 5-HT(1A) autoreceptors but not heteroreceptors after treatment with 5-HT(1A) receptor agonist. They suggest that this desensitization is the result of autoreceptor internalization.