DOPAMINE TRANSPORTER MESSENGER-RNA LEVELS ARE HIGH IN MIDBRAIN NEURONS VULNERABLE TO MPTP

THE neurotoxin MPTP kills only certain midbrain dopaminergic (DA) neur ons to produce a model of Parkinson's disease. The dopamine transporte r (DAT) is important to MPTP toxicity because to be neurotoxic, an MPT P metabolite must first gain access to the DA neuron via the DAT. Also , MPTP is less toxic to DA neurons that contain the putative neuroprot ective calcium-binding protein calbindin-D-28k (CB). The present study examined the relative importance of DAT activity and CB for cellular vulnerability to MPTP-induced degeneration in the C57BL/6 mouse. Cells that were vulnerable to MPTP were found to contain high levels of DAT mRNA, whereas cells that were not vulnerable contained low levels. Al so, the few substantia nigra cells remaining after a toxic dose of MPT P contained only low levels of DAT mRNA. However, there was not a stro ng relationship between cellular resistance to MPTP toxicity and cells containing CB. These data provide in vivo evidence for a direct corre lation between midbrain cellular vulnerability to MPTP toxicity and th e activity of the DAT.