Validity of a quantitative technique to study striatal dopaminergic neurodegeneration by in vivo microdialysis

The development of a technique that allows the direct quantitative study of the damage produced by a toxin on a specific neurotransmitter system is ve ry important. For that, we have used the microdialysis technique to validat e a method to study the specific drug's toxicity on dopaminergic (DAergic) striatal terminals. We perfused different MPP+ and 6-hydroxydopamine (6-OHD A) concentrations, with different toxicity for DAergic terminals, 24 h afte r the implantation of the microdialysis probe (day 1). One day later (day 2 ), MPP+ was perfused through the microdialysis probe and DA extracellular o utput measured. We hypothesize that the amount of extracellular dopamine (D A) obtained on day 2 is directly proportional to the neurotoxic damage prod uced on day 1. To corroborate this hypothesis tyrosine hydroxylase (TH) imm unohistochemistry was also carried out on day 2. There was a clear correlat ion index between the amount of DA measured after MPP+ perfusion and the la ck of TH immunoreactivity measured as the radius of the area showing decrea se in TH immunoreactivity around the cannula. These results show the possib ility to measure DAergic remaining terminals after a toxic drug exposure by in vivo MPP+ perfusion. The possibility to extend this neurotoxic study to another neurotransmitter systems is suggested. (C) 2001 Elsevier Science B .V. All rights reserved.