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

Neuropsychopharmacology. 2008 Sep;33(10):2427-34. doi: 10.1038/sj.npp.1301644. Epub 2007 Dec 12.

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-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.

MeSH terms

  • 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

Substances

  • 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
  • Dioxanes
  • Oxadiazoles
  • Piperidines
  • RS 39604
  • Serotonin 5-HT4 Receptor Agonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptors, Serotonin, 5-HT4
  • Serotonin
  • Propane