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Nigral and Striatal Comparative Study of the Neurotoxic Action of 1‐Methyl‐4‐Phenylpyridinium Ion: Involvement of Dopamine Uptake System
Author(s) -
Santiago Marti,
Machado Alberto,
Cano Josefina
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66031182.x
Subject(s) - nomifensine , dopamine , striatum , substantia nigra , microdialysis , chemistry , basal ganglia , 3,4 dihydroxyphenylacetic acid , endocrinology , medicine , mptp , dopaminergic , biology , homovanillic acid , biochemistry , central nervous system , serotonin , receptor
Microdialysis was used in a comparative study of the neurotoxic action of MPP + in the absence or presence of nomifensine (20 µ M ) in the striatum and substantia nigra. Three different concentrations of MPP + (1, 2.5, and 5 m M ) were perfused for 15 min at 24 (day 1) and 48 h (day 2) after surgery. The dopamine basal value in the striatum was ∼17 fmol/min. Nomifensine (20 µ M ) stimulated dopamine release to ∼170 fmol/min. The increase of dopamine extracellular output in the striatum after MPP + perfusion on day 1 was independent of the concentration of MPP + perfused and of the absence or presence of nomifensine (20 µ M ), being ∼2,500 fmol/min. The dopamine basal value in the substantia nigra was below the detection limit of our HPLC equipment. Nomifensine (20 µ M ) stimulated dopamine release to ∼6.3 fmol/min. The increase of dopamine extracellular output in the substantia nigra was MPP + dose‐dependent (1 m M , 75 fmol/min; 2.5 m M , 150 fmol/min; and 5 m M , 250 fmol/min) and independent of the presence or absence of nomifensine. On day 2, the presence of nomifensine on day 1 produced a total protection against MPP + (1 m M ) perfusion in the striatum, which was not observed against MPP + (5 m M ). MPP + (1 m M ) did not produce any neurotoxic action in the substantia in the absence or presence of nomifensine. The MPP + (2.5 m M ) effect on dopamine extracellular output in the absence of nomifensine (20 µ M ) in the substantia nigra on day 2 was similar to that of MPP + (1 m M ) in the striatum. The presence of nomifensine (20 µ M ) partially prevented the neurotoxic effect of MPP + (2.5 m M ) on dopaminergic cell bodies/dendrites in the substantia nigra. The MPP + (5 m M ) effect on dopamine extracellular output was similar in both structures studied in the absence or presence of nomifensine on day 2. These results suggest that terminals in the striatum are more sensitive to the neurotoxicity of MPP + than cell bodies/dendrites in the substantia nigra.