Acute effects of intranigral application of MPP+ on nigral and bilateral striatal release of dopamine simultaneously recorded by microdialysis.
Intracerebral microdialysis in freely moving rats was used to investigate the effects of perfusions with the 1-methyl-4-phenylpyridinium ion (MPP+) in the substantia nigra (SN) on the extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the perfused SN and in the ipsi- and contralateral striata. Following MPP+ perfusion, the release of DA in the SN increased markedly from nondetectable basal levels to about 105 fmoles/min, whereas the output of DOPAC, HVA and 5-HIAA decreased below 25% of basal levels. The intranigral MPP+ application induced, at the same time, an almost immediate, long-lasting decrease in the release of DA in the ipsilateral striatum to less than 20% of basal levels and a moderate increase in the DOPAC and HVA levels, without affecting 5-HIAA output. In the contralateral striatum, the extracellular levels of DA, DOPAC, HVA and 5-HIAA remained unchanged during the entire perfusion experiment. These results suggest that infusion of 10 mM MPP+ into the SN produces an almost immediate blockade of neuronal impulse flow, as shown by the rapid decline in DA release from the ipsilateral striatal nerve terminals. The simultaneously occurring massive increase of the extracellular DA in the SN is, therefore, probably the result of destruction of the nigral cell bodies and/or dendrites following locally applied MPP+. This study clearly illustrates the possibilities of simultaneous microdialysis in various brain areas, allowing pharmacological manipulations on the levels of the cell bodies, while monitoring events in the terminal areas.
Santiago
M
M
Department of Medicinal Chemistry, University Centre for Pharmacy, Groningen, The Netherlands.
Rollema
H
H
de Vries
J B
JB
Westerink
B H
BH
D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid