Differential Regulation of Somatodendritic Serotonin 5-HT1AReceptors by 2-Week Treatments with the Selective Agonists Alnespirone (S-20499) and 8-Hydroxy-2-(Di-n-Propylamino)tetralin
| Autor: | Guadalupe Mengod, Josep Casanovas, Francesc Artigas, M. T. Vilaró |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Agonist Serotonin medicine.medical_specialty Microdialysis medicine.drug_class 5-Hydroxytryptamine (5-HT) release Gene Expression Anxiety Biochemistry Frontal cortex Radioligand Assay Cellular and Molecular Neuroscience chemistry.chemical_compound Dorsal raphe nucleus Internal medicine polycyclic compounds medicine Animals Alnespirone Spiro Compounds heterocyclic compounds RNA Messenger Rats Wistar Receptor In Situ Hybridization Brain Chemistry 8-Hydroxy-2-(di-n-propylamino)tetralin Dose-Response Relationship Drug Depression Chemistry musculoskeletal neural and ocular physiology Dendrites Frontal Lobe Rats Serotonin Receptor Agonists Endocrinology nervous system Receptors Serotonin Autoradiography Raphe Nuclei Serotonin 5-HT1A receptors Raphe nuclei Receptors Serotonin 5-HT1 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0022-3042 |
| Popis: | Single treatment with the serotonin (5-hydroxytryptamine) 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and alnespirone (S-20499) reduces the extracellular 5-HT concentration (5-HText) in the rat midbrain and forebrain. Given the therapeutic potential of selective 5-HT1A agonists in the treatment of affective disorders, we have examined the changes in 5-HT1A receptors induced by 2-week minipump administration of alnespirone (0.3 and 3 mg/kg/day) and 8-OH-DPAT (0.1 and 0.3 mg/kg/day). The treatment with alnespirone did not modify baseline 5-HText but significantly attenuated the ability of 0.3 mg/kg s.c. alnespirone to reduce 5-HText in the dorsal raphe nucleus (DRN) and frontal cortex. In contrast, the ability of 8-OH-DPAT (0.025 and 0.1 mg/kg s.c.) to reduce 5-HText in both areas was unchanged by 8-OH-DPAT pretreatment. Autoradiographic analysis revealed a significant reduction of [3H]8-OH-DPAT and [3H]WAY-100635 {3H-labeled N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide · 3HCl} binding to somatodendritic 5-HT1A receptors (but not to postsynaptic 5-HT1A receptors) of rats pretreated with alnespirone but not with 8-OH-DPAT. In situ hybridization analysis revealed no change of the density of the mRNA encoding the 5-HT1A receptors in the DRN after either treatment. These data indicate that continuous treatment for 2 weeks with alnespirone, but not with 8-OH-DPAT, causes a functional desensitization of somatodendritic 5-HT1A receptors controlling 5-HT release in the DRN and frontal cortex. |
| Databáze: | OpenAIRE |
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