Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain
| Autor: | Pierre-Alain Boyer, Naïma Hanoun, Elisabeth Mocaer, Laurence Lanfumey, Michel Hamon |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Action Potentials Serotonin 5-HT1 Receptor Antagonists Pharmacology Rats Sprague-Dawley Cellular and Molecular Neuroscience Dorsal raphe nucleus Fluoxetine Internal medicine Acetamides medicine Animals Agomelatine Melatonin receptor agonist 5-HT receptor Dose-Response Relationship Drug Chemistry Ipsapirone Brain Receptor antagonist Antidepressive Agents Rats Endocrinology Receptor Serotonin 5-HT1A Serotonin Protein Binding medicine.drug |
| Zdroj: | Neuropharmacology. 47:515-526 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2004.06.003 |
| Popis: | Agomelatine (S 20098) is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties, but actual mechanisms underlying its antidepressant action are unknown. Because functional desensitization of 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) occurs after chronic administration of several classes of antidepressants, we investigated whether this adaptive change could also be induced by agomelatine. Neither acute nor chronic treatment with agomelatine (10 mg/kg i.p. for 14 days or 50 mg/kg i.p. for 21 days) changed the density of 5-HT(1A) receptors and their coupling with G proteins in the DRN and the hippocampus in rats. Moreover, these treatments did not affect the basal electrophysiological characteristics and the responses to 5-HT(1A) receptor stimulation of DRN and hippocampal neurons in brain slices. Parallel experiments with melatonin (10 mg/kg i.p. for 14 days) and fluoxetine (5 mg/kg i.p. for 14 days) as reference compounds showed that the former was unable to affect 5-HT(1A) receptors whereas the latter decreased both the 5-HT(1A) receptor-mediated [(35)S]GTP-gamma-S binding and the potency of ipsapirone, a 5-HT(1A) receptor agonist, to inhibit neuronal firing in the DRN. These data indicate that the antidepressant action of agomelatine is not mediated through the same mechanisms as SSRIs or tricyclics. |
| Databáze: | OpenAIRE |
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