Oseltamivir enhances hippocampal network synchronization

J Pharmacol Sci. 2008 Apr;106(4):659-62. doi: 10.1254/jphs.sc0070467. Epub 2008 Apr 9.

Abstract

Oseltamivir, a widely used anti-influenza drug, inhibits virus neuraminidase. A mammalian homologue of this enzyme is expressed in the brain, yet the effect of oseltamivir on central neurons is largely unknown. Patch-clamp recordings ex vivo revealed that oseltamivir enhanced spike synchronization between hippocampal CA3 pyramidal cells. Time-lapse multineuron calcium imaging revealed that oseltamivir and its active metabolite evoked synchronized population bursts that recruited virtually all neurons in the network. This unique, so-far-unknown, event was attenuated by muscarinic receptor antagonist. Thus, oseltamivir is a useful tool for investigating a new aspect of neural circuit operation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Antiviral Agents / pharmacology*
  • Calcium Signaling / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Microscopy, Fluorescence
  • Muscarinic Antagonists / pharmacology
  • Nerve Net / drug effects*
  • Nerve Net / enzymology
  • Neuraminidase / antagonists & inhibitors*
  • Oseltamivir / pharmacology*
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / enzymology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Tissue Culture Techniques

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Muscarinic Antagonists
  • Oseltamivir
  • Neuraminidase