Mireille Meunier

Riluzole and experimental parkinsonism : antagonism of MPTP-induced decrease in central dopamine levels in mice

We have investigated whether riluzole, a compound that interferes with glutamatergic (GLUergic) transmission, would protect central dopaminergic (DAergic) neurones from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the striatum in mice. MPTP decreased DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Riluzole protected against the MPTP-induced decrease in DA levels. The utilization of DA ([DOPAC+HVA]/DA) was increased after MPTP treatment, but returned to control values in mice given riluzole in combination with MPTP. Riluzole did not confer protection by inhibiting either monoamine oxidase type B activity or DA uptake. Possible mechanisms involved in the protective action of riluzole are discussed. Our results show that riluzole antagonizes the DAergic neurotoxicity of MPTP, a pro-parkinsonian neurotoxin, in mice.

Riluzole and experimental parkinsonism : partial antagonism of MPP+-induced increase in striatal extracellular dopamine in rats in vivo

SUPERFUSION of the rat striatum with 100 μM of 1-methyl-4-phenylpyridinium (MPP+) induced a 70-fold increase in dopamine (DA) release and a decrease in the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Pretreatment with riluzole (8 mg kg-1, i.p.), a compound that interferes with glutamatergic transmission, partially antagonized the effect of MPP+ on the release of DA, but did not change the effects of this toxin on the efflux of DOPAC and HVA. Riluzole did not affect the increase in DA release induced by MPP+ in vitro. The in vivo efficacy of riluzole on MPP+-induced DA release could be due to its central interference with glutamatergic transmission. Our data point to a protective role of riluzole with regard to DA release, a marker of the neuronal impairment induced by MPP+, a pro-parkinsonian neurotoxin.

Pharmacology: Ouabain-induced Increase in Dopamine Release from Mouse Striatal Slices is Antagonized by Riluzole

We have examined the effects of riluzole, a neuroprotective drug which stabilizes voltage‐dependent sodium channels in their inactivated state and inhibits the release of glutamate in‐vivo and in‐vitro, on the release of newly taken up [3H]dopamine induced by ouabain, a potent and selective inhibitor of Na+/K+‐ATPase in mouse striatal slices in‐vitro.

3-Nitropropionic acid exacerbates [3H]GABA release evoked by glucose deprivation in rat striatal slices.

3−Nitropropionic acid (3−NPA) is a metabolic poison that produces lesions of striatal intrinsic neurones such as γ‐aminobutyric acid (GABA) neurones. This study was carried out to determine whether 3−NPA would impair the ability of striatal GABAergic neurones to withstand hypoglycaemic stress.