The acute convulsant effect of MPTP is dependent on intracerebral MPP +

Abstract

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57 black mice causes an acute seizure syndrome the severity of which is dose dependent; there is also a good correlation between the seizure inducing potential of MPTP and the neostriatal dopamine (DA) depletion caused by MPTP. The simultaneous administration of MPTP and MAO B inhibitors attenuates both epileptiform phenomena and neostriatal DA depletion. On the contrary diethyldithiocarbamate (DDC) exacerbates both responses. All these pharmacological manipulations are known to affect the accumulation of 1-methyl-4-phenylpyridinium ion (MPP +) the main metabolite of MPTP. Thus the present data support the hypothesis of a strict dependence of the epileptiform phenomena on the presence of MPP +. Furthermore the tight correlation existing between the severity of epileptic events and DA depletion suggests that the acute excitotoxic syndrome may contribute to the long-term toxicity of MPTP. On leave from the Department of Neurology, University of Pisa, Pisa, Italy.