Serotonin1B heteroreceptor activation induces an antidepressant-like effect in mice with an alteration of the serotonergic system

Franck Chenu; Denis J.P. David; Isabelle Leroux-Nicollet; Erwan Le Maître; Alain M. Gardier; Michel Bourin

doi:10.1139/jpn.0852

journal article Nov 01, 2008

Serotonin1B heteroreceptor activation induces an antidepressant-like effect in mice with an alteration of the serotonergic system

Franck Chenu Denis J.P. David Isabelle Leroux-Nicollet Erwan Le Maître Alain M. Gardier Michel Bourin

Journal of Psychiatry and Neuroscience Vol. 33 No. 6 pp. 541-550 · Canadian Science Publishing

View at Publisher Save 10.1139/jpn.0852

Abstract

Objective: We sought to demonstrate whether the specific activation of serotonin1B (5-HT1B) heteroreceptors by systemic or local administration of the selective 5-HT1B receptor agonist anpirtoline could mediate antidepressant-like effects in mice. Methods: We confirmed the selectivity of action of anpirtoline in the forced swim test (FST) in 5-HT1B knockout mice. We then evaluated the behavioural effects of anpirtoline on 5-HT–lesioned (5,7-dihydroxytryptamine creatinine [5,7-DHT]) and 5-HT–depleted (p-CPA) mice. We estimated the depletion level and selectivity of action of 5,7-DHT and p-CPA by measuring the neurotransmitter levels and [3H]-citalopram binding. We investigated the antidepressant-like effect of anpirtoline when locally perfused in an area of the brain where the response is mainly attributable to presynaptic (cortex and hippocampus) or postsynaptic receptors (substantia nigra and caudate putamen). Furthermore, we evaluated the effect of the 5-HT1B receptor antagonist GR127935 on the activity of various antidepressants in the FST. Results: Anpirtoline was devoid of effects in 5-HT1B receptor knockout mice. It induced a greater effect in p-CPA and 5,7-DHT pretreated mice compared with control subjects, suggesting that the antidepressant-like activity of anpirtoline mainly depends on 5-HT1B heteroreceptor stimulation (autoreceptors being destroyed by 5,7-DHT). This observation was confirmed by the results showing the antidepressant-like effect of anpirtoline when locally perfused in areas of the brain that contain postsynaptic receptors. The blockade of 5-HT1B receptors antagonizes the effect of selective serotonin reuptake inhibitors (SSRIs). Conclusion: Our results demonstrate that the antidepressant-like effect of SSRIs in the FST requires the activation of 5-HT1B heteroreceptors.

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Details

Published: Nov 01, 2008
Vol/Issue: 33(6)
Pages: 541-550
License: View

Authors

F

Franck Chenu

Neurobiologie de l’anxiété et de la dépression, Faculté de Médecine, Université de Nantes, Nantes

D

Denis J.P. David

Sérotonine et Neuropharmacologie, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry

I

Isabelle Leroux-Nicollet

Unité de Neuropsychopharmacologie, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France

E

Erwan Le Maître

Unité de Neuropsychopharmacologie, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France

A

Alain M. Gardier

Sérotonine et Neuropharmacologie, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry

M

Michel Bourin

Neurobiologie de l’anxiété et de la dépression, Faculté de Médecine, Université de Nantes, Nantes

Cite This Article

Franck Chenu, Denis J.P. David, Isabelle Leroux-Nicollet, et al. (2008). Serotonin1B heteroreceptor activation induces an antidepressant-like effect in mice with an alteration of the serotonergic system. Journal of Psychiatry and Neuroscience, 33(6), 541-550. https://doi.org/10.1139/jpn.0852

Serotonin1B heteroreceptor activation induces an antidepressant-like effect in mice with an alteration of the serotonergic system

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