Neurochemical lesioning in the rat brain with iontophoretic injection of the 1-methyl-4-phenylpyridinium ion (MPP +)

Iontophoretic injections of the 1-methyl-4-phenylpyridinium ion (MPP +) were made in the dopaminergic part of the substantia nigra to see whether this injection technique could be used for inducing localized neurochemical lesions in dopaminergic cell groups and to assess the effects of MPP + on non-dopaminergic neurons. Three days after the iontophoretic injection of MPP +, a gliosis or necrotic hole was found in the dopaminergic and non-dopaminergic target areas. This effect depended on the injection parameters that were used; iontophoretic injections of short duration (≤ 3 minutes) and low current strength (1.5 μA) caused the gliosis, higher injection parameters gave lesions. The estimated injected amount of MPP + was between 0.5 and 10.8 nmol. Control injections, with sodium iodide, sodium chloride or N-methylpyridinium iodide showed that the neurodegeneration is not a side-effect of the iontophoretic injection procedure. It is concluded that iontophoretically injected MPP + is toxic for all neurons, irrespective of the neurotransmitter used, and also for glia cells and fibers of passage. Excessive formation of free radicals, causing induction of lipid peroxidation, may be involved in the neurodegenerative process observed.