title: Pharmacological blockade of 5-HT7 receptors as a putative fast acting antidepressant strategy.
abstract: 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.
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon 1, Faculty of Pharmacy, Laboratoire de Neuropharmacologie, CNRS EAC 5006, Lyon, France.
authors.forename: Ouissame
authors.initials: O
authors.lastname: Mnie-Filali
authors.forename: Céline
authors.initials: C
authors.lastname: Faure
authors.forename: Laura
authors.initials: L
authors.lastname: Lambás-Señas
authors.forename: Mostafa
authors.initials: M
authors.lastname: El Mansari
authors.forename: Hassina
authors.initials: H
authors.lastname: Belblidia
authors.forename: Elise
authors.initials: E
authors.lastname: Gondard
authors.forename: Adeline
authors.initials: A
authors.lastname: Etiévant
authors.forename: Hélène
authors.initials: H
authors.lastname: Scarna
authors.forename: Anne
authors.initials: A
authors.lastname: Didier
authors.forename: Anne
authors.initials: A
authors.lastname: Berod
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
authors.forename: Nasser
authors.initials: N
authors.lastname: Haddjeri
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor