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.