The protective effect of riluzole in the MPTP model of Parkinson's diseasein mice is not due to a decrease in MPP+ accumulation

Riluzole, has previously been shown to be protective in animal models of Pa rkinson's disease in vivo. In the present study the: effects of riluzole on thr intrastriatal formation and accumulation of MPP+, after i.p, injection of MPTP were tested in mice. using two different experimental protocols. I n the first protocol, mice were treated with a single dose (15 mg/kg i.p.) of MPTP and MPP+ accumulation was measured 30 mint 1 h and 3 h after the in jection of the toxin. Riluzole (10 mg/kg p.o.) administered 30 min before M PTP. did not modify the accumulation kinetic of MPP+. Contrarily to riluzol e. a single dose of 50 mg/kg p.o. of 7-nitroindazole (7-NI). a non-selectiv e non hypertensive inhibitor of nitric oxide: synthase (NOS), significantly decreased MPP+ levels, In the second protocol, consisting of 3 injections of MPTP (15 mg/kg i.p.), riluzole, administered 1 times at the dose of 5 mg /kg p.o., had no effect on MPP+ levels. The protective effect of repeated t reatments of riluzole and 7-NI against MPTP-induced depletion of dopamine ( DA) is also reported. Our data obtained with 7-NI tin agreement with previo us studies reported by others) suggest that a part of the protection observ ed with this NOS inhibitor is probably due to in vivo inhibition of monoami ne oxidase-B (MAO-B. That riluzole does not modify MPP+ accumulation demons trates that its protective affect against MPTP toxicity was not due to an i n vivo interference with MPTP metabolism. (C) 2000 Elsevier Science Ltd, Al l rights reserved.