Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP

• Published in: Journal of neural transmission Vol. 74; no. 2; p. 75
• Main Authors: Sun, C J, Johannessen, J N, Gessner, W, Namura, I, Singhaniyom, W, Brossi, A, Chiueh, C C
• Format: Journal Article
• Language: English
• Published: Austria 01.06.1988
• Subjects: 1-Methyl-4-phenylpyridinium; Amphetamines - pharmacology; Animals; Apomorphine - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiology; Dopamine - metabolism; Male; Piperazines - pharmacology; Pyridinium Compounds - toxicity; Rats; Rats, Inbred Strains; Stereotyped Behavior - drug effects; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - physiology
• DOI: 10.1007/bf01245141

Unilateral intranigral administration of the oxidative metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenyl-dihydropyridine (MPDP+) or 1-methyl-4-phenylpyridine (MPP+) produced dose-dependently a depletion of dopamine in the ipsilateral striatum of rats two weeks following treatment. d-Amphetamine and apomorphine induced circling toward the lesioned side in these unilaterally treated animals. No contralateral circling behavior was observed after challenging with apomorphine. This dopamine lesioning effect of MPP+ was not blocked by pretreatment of animals with a dopamine uptake blocker, GBR 12909. Furthermore, MPP+ increased the 45Ca accumulation into cells at the site of injection and produced "nonspecific" cell membrane and/or cytotoxic damage seen by histological procedures. These results indicate that MPDP+ and MPP+ produced localized cytotoxic damage to nigrostriatal neurons, caused a decrease in striatal dopamine, and disrupted the nigrostriatal system's functioning following intranigral administration to rats. It is postulated that the cationic surfactant properties of MPDP+ and MPP+ might contribute to its neurotoxic effects.