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The promnesic effect of G-protein-coupled 5-HT4 receptors activation is mediated by a potentiation of learning-induced spine growth in the mouse hippocampus
Article de revue scientifique   Avec comité de lecture

The promnesic effect of G-protein-coupled 5-HT4 receptors activation is mediated by a potentiation of learning-induced spine growth in the mouse hippocampus

Leonardo Restivo, François Roman, Aline Dumuis, Joel Bockaert, Evelyne Marchetti et Martine Ammassari-Teule
Neuropsychopharmacology (New York, N.Y.), Vol.33(10), p.2427-2434
01/09/2008
DOI: https://doi.org/10.1038/sj.npp.1301644
PMID: 18075492

Résumé

Animals Dendritic Spines - drug effects Dendritic Spines - metabolism Dendritic Spines - ultrastructure Dioxanes - pharmacology Discrimination Learning - drug effects Discrimination Learning - physiology Drug Interactions - physiology Hippocampus - drug effects Hippocampus - metabolism Hippocampus - ultrastructure Learning - drug effects Learning - physiology Male Memory - drug effects Memory - physiology Mice Mice, Inbred C57BL Neuronal Plasticity - drug effects Neuronal Plasticity - physiology Oxadiazoles - pharmacology Piperidines - pharmacology Propane - analogs & derivatives Propane - pharmacology Receptors, Serotonin, 5-HT4 - metabolism Serotonin - metabolism Serotonin 5-HT4 Receptor Agonists Serotonin Antagonists - pharmacology Serotonin Receptor Agonists - pharmacology Synaptic Transmission - drug effects Synaptic Transmission - physiology
Pharmacological modulation of synaptic efficacy is a prominent target in the identification of promnesic compounds. Here, we report that pretraining administration of the serotonin 5-HT(4) receptors (5-HT(4)Rs) partial agonist SL65.0155 enhances simultaneous olfactory discrimination performance and potentiates learning-induced dendritic spine growth in the mouse hippocampus. SL65.0155 does not affect spine density in the pseudo-trained mice and, by itself, does not promote spine growth. Injecting the 5-HT(4) antagonist RS39604 prior to SL65.0155 prevents both the increase in performance and the additional formation of spines, thus confirming the 5-HT(4)Rs specificity of the observed effects. These findings provide evidence that 5-HT(4)Rs stimulation selectively increases experience-dependent structural plasticity in learning-activated hippocampal circuits.

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