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Responsiveness of Striatal Dopamine Release in Awake Animals After Chronic 1‐Methyl‐4‐Phenylpyridinium Ion‐Induced Lesions of the Substantia Nigra
Author(s) -
Santiago M.,
Westerink B. H. C.,
Rollema H.
Publication year - 1991
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 - 10.1111/j.1471-4159.1991.tb11430.x
Subject(s) - substantia nigra , dopamine , neuroscience , chemistry , endocrinology , medicine , basal ganglia , pharmacology , biology , dopaminergic , central nervous system
Extracellular concentrations of dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), and homovanillic acid were measured by microdialysis in rat striatum 1 month after a unilateral infusion via a dialysis probe of a high concentration (10 m M ) of 1‐methyl‐4‐phenylpyridinium ion (MPP + ) into the substantia nigra. The basal extracellular DA concentration at the lesioned side was about 20% of the concentration at the nonlesioned side. However, basal DOPAC dialysate levels from the lesioned striatum represented only 2.4% of those from the contralateral side. Intrastriatal infusion with nomifensine increased the dialysate content of DA about twofold and eightfold at the lesioned and nonlesioned sides, respectively. Co‐infusion of nomifensine with (–)‐sulpiride caused an additional pronounced rise of the DA output on top of the nomifensine‐induced increase at the nonlesioned side, whereas no effect was observed at the lesioned side. Finally, MPP + (10 m M ) was infused for 45 min into both striata. The increase in the dialysate content of DA in response to MPP + (considered as an index of the total striatal DA content) from the lesioned side was only 0.6% of the MPP + ‐induced DA increase from the nonlesioned side. A strong compensatory response to increased extracellular dopamine was observed in the ipsilateral striatum. This effect was achieved by a severe suppression of reuptake mechanisms, as well as of the autoreceptor feedback response. It is concluded that infusion of MPP + into the substantia nigra can be used as a chronic biochemical model for clinically manifest parkinsonism.