Electrophysiology of the neuroprotective agent riluzole on striatal spiny neurons

Diego Centonze, Paolo Calabresi, Antonio Pisani, Silvia Marinelli, Girolama Alessandra Marfia, Giorgio Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

Striatal spiny neurons are selectively vulnerable in Huntington's disease (HD). No effective treatment is available to limit neuronal death in this pathological condition. In an experimental model of HD, a beneficial effect has recently been reported by the neuroprotective agent riluzole. We performed intracellular recordings in order to characterize the electrophysiological effects of this compound on striatal spiny neurons. Riluzole (0.1-100 μM) affected neither the resting membrane potential nor the input resistance/membrane conductance of the recorded cells. Bath application of this pharmacological agent produced a dose-dependent reduction of the number of spikes evoked by long-lasting depolarizing pulses. The EC50 value for this effect was 0.5 μM. Low doses of riluzole selectively reduced the firing frequency in the last part of the depolarizing pulse suggesting a use-dependent action at low concentrations of this compound. Riluzole produced a dose-dependent reduction of the amplitude of the corticostriatal glutamatergic excitatory post-synaptic potentials (EPSPs) with an extrapolated EC50 value of 6 μM. This effect was reversible and maximal at a concentration of 100 μM. Paired-pulse facilitation (PPF) was not affected by riluzole suggesting that the reduction of excitatory transmission was not only caused by a decrease of presynaptic release. Accordingly, riluzole also reduced the amplitude of membrane depolarization induced by exogenous glutamate. The modulatory action of riluzole on the activity of striatal spiny neurons might support the use of this drug in experimental models of excitotoxicity and in the neurodegenerative disorders involving the striatum. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1063-1070
Number of pages8
JournalNeuropharmacology
Volume37
Issue number8
DOIs
Publication statusPublished - Aug 1998

Keywords

  • Excitatory amino acids
  • Huntington disease
  • Intracellular recordings
  • Striatum
  • Synaptic transmission

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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