Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy
| Autor: | Adeline Etievant, Elise Gondard, Mostafa El Mansari, Laura Lambás-Señas, Pierre Blier, H. Scarna, Céline Faure, Nasser Haddjeri, Anne Didier, Anne Bérod, Ouissame Mnie-Filali, Hassina Belblidia |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Pharmacology Rats Sprague-Dawley Phenols Internal medicine Reaction Time medicine Animals Serotonin Antagonists 5-HT receptor Neuropharmacology Depressive Disorder Sulfonamides Fluoxetine Receptor antagonist Antidepressive Agents Rats Disease Models Animal Psychiatry and Mental health Endocrinology Receptors Serotonin Antidepressant Original Article Serotonin Psychology medicine.drug Behavioural despair test |
| Zdroj: | Neuropsychopharmacology. 36:1275-1288 |
| ISSN: | 1740-634X 0893-133X |
| Popis: | Current antidepressants still display unsatisfactory efficacy and a delayed onset of therapeutic action. Here we show that the pharmacological blockade of serotonin 7 (5-HT(7)) receptors produced a faster antidepressant-like response than the commonly prescribed antidepressant fluoxetine. In the rat, the selective 5-HT(7) receptor antagonist SB-269970 counteracted the anxiogenic-like effect of fluoxetine in the open field and exerted an antidepressant-like effect in the forced swim test. In vivo, 5-HT(7) receptors negatively regulate the firing activity of dorsal raphe 5-HT neurons and become desensitized after long-term administration of fluoxetine. In contrast with fluoxetine, a 1-week treatment with SB-269970 did not alter 5-HT firing activity but desensitized cell body 5-HT autoreceptors, enhanced the hippocampal cell proliferation, and counteracted the depressive-like behavior in olfactory bulbectomized rats. Finally, unlike fluoxetine, early-life administration of SB-269970, did not induce anxious/depressive-like behaviors in adulthood. Together, these findings indicate that the 5-HT(7) receptor antagonists may represent a new class of antidepressants with faster therapeutic action. |
| Databáze: | OpenAIRE |
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