ELECTROPHYSIOLOGY OF THE NEUROPROTECTIVE AGENT RILUZOLE ON STRIATAL SPINY NEURONS

Striatal spiny neurons are selectively vulnerable in Huntington's dise ase (HD). No effective treatment is available to limit neuronal death in this pathological condition. In an experimental model of HD, a bene ficial effect has recently been reported by the neuroprotective agent riluzole. We performed intracellular recordings in order to characteri ze the electrophysiological effects of this compound on striatal spiny neurons. Riluzole (0.1-100 mu M) affected neither the resting membran e potential nor the input resistance/membrane conductance of the recor ded cells. Bath application of this pharmacological agent produced a d ose-dependent reduction of the number of spikes evoked by long-lasting depolarizing pulses. The EC,, value for this effect was 0.5 mu M. Low doses of riluzole selectively reduced the firing frequency in the las t part of the depolarizing pulse suggesting a use-dependent action at low concentrations of this compound. Riluzole produced a dose-dependen t reduction of the amplitude of the corticostriatal glutamatergic exci tatory post-synaptic potentials (EPSPs) with an extrapolated EC50 valu e of 6 mu M. This effect was reversible and maximal at a concentration of 100 mu M. Paired-pulse facilitation (PPF) was not affected by rilu zole suggesting that the reduction of excitatory transmission was not only caused by a decrease of presynaptic release. Accordingly, riluzol e also reduced the amplitude of membrane depolarization induced by exo genous glutamate. The modulatory action of riluzole on the activity of striatal spiny neurons might support the use of this drug in experime ntal models of excitotoxicity and in the neurodegenerative disorders i nvolving the striatum. (C) 1998 Elsevier Science Ltd. All rights reser ved.