Abstract
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-HT4 receptors (5-HT4Rs) 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-HT4 antagonist RS39604 prior to SL65.0155 prevents both the increase in performance and the additional formation of spines, thus confirming the 5-HT4Rs specificity of the observed effects. These findings provide evidence that 5-HT4Rs stimulation selectively increases experience-dependent structural plasticity in learning-activated hippocampal circuits.
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The authors thank the three anonymous reviewers for their helpful criticism and comments on this paper.
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The authors declare that, except for income from their primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
Supplementary Information accompanies the paper on the Neuropsychopharmacology website (http://www.nature.com/npp)
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Restivo, L., Roman, F., Dumuis, A. et al. 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. Neuropsychopharmacol 33, 2427–2434 (2008). https://doi.org/10.1038/sj.npp.1301644
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DOI: https://doi.org/10.1038/sj.npp.1301644
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