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.
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.
Restivo
Leonardo
L
CNR Institute for Neuroscience, Rome, Italy.
Roman
François
F
Dumuis
Aline
A
Bockaert
Joel
J
Marchetti
Evelyne
E
Ammassari-Teule
Martine
M
D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004146:Dioxanes / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives / Q000494:pharmacology; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058828:Serotonin 5-HT4 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C464499:5-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-(1-(2-phenylethyl)-4-piperidinyl)-1,3,4-oxadiazol-2(3H)-one; D004146:Dioxanes; D010069:Oxadiazoles; D010880:Piperidines; C475107:RS 39604; D058828:Serotonin 5-HT4 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D011407:Propane