The influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the levels of dopamine, serotonin and their metabolites in the caudate nucleus of the rat.
Until now it has been generally believed that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) could induce a Parkinson-like syndrome only in man and in the rhesus monkey, a syndrome which begins with degeneration of the nigrostriatal system and is accompanied by a marked reduction in dopamine levels in the caudate nucleus. Rats, guinea pigs and cats subjected to comparable doses of NMPTP showed neither motor nor biochemical disturbances. In the present study it could be demonstrated, however, that long-term treatment of rats with a total dose of 116.9 mg NMPTP/kg brings about changes in the metabolism of the biogenic amines dopamine and serotonin in the caudate nucleus. The treatment reduced the dopamine and homovanillic acid levels to about 50% of their normal values, 3.4-dihydroxyphenylacetic acid also to 60% of the control levels. These experiments demonstrate that NMPTP, given in appropriate doses for a sufficient time, is capable of producing neurodegenerative changes in rats as well. This implies that the rat is a suitable experimental animal for studies with NMPTP.
Russ
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Henning
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Eckhardt
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Przuntek
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H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011725:Pyridines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid