Comparison of the effects of intracerebrally administered MPP+ (1-methyl-4-phenylpyridinium) in three species: microdialysis of dopamine and metabolites in mouse, rat and monkey striatum.
Intracerebral microdialysis in 3 awake species allowed the measurement of the basal output of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) from rat and mouse striatum and monkey caudate in vivo. The DOPAC/HVA ratios in dialysates from mouse and rat striatum were about 1 and 2 respectively, but only 0.09 in monkey caudate dialysates. The extracellular levels of the metabolites correlated well with reported tissue levels, while extracellular DA levels were 3 orders of magnitude lower than tissue concentrations. The effects of the intracerebrally administered dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) were essentially similar in the 3 species. In all cases an immediate, massive release of DA was accompanied by a pronounced decrease in the output of the metabolites. Basal DA release was no longer detectable 5-12 h after MPP+ administration and a second MPP+ perfusion failed to increase the release of DA.
Rollema
H
H
Division of Toxicology, School of Pharmacy, University of California, San Francisco 94143.
Alexander
G M
GM
Grothusen
J R
JR
Matos
F F
FF
Castagnoli
N
N
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D015102:3,4-Dihydroxyphenylacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid