Effect of intraventricular injection of 1-methyl-4-phenylpyridinium: protection by acetyl-L-carnitine.
1-methyl-4-phenylpyridinium (MPP+) is the bioactivated product of 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridine (MPTP). The neurotoxic action of MPP+ injected intracerebroventricularly (ICV) in the rat has been studied, using dopaminergic systems in the substantia nigra, striatum, olfactory bulb, median eminence and hypophysis. The following results were obtained: (1) Rats with ICV administration of 1 microliter MPP+ solution (62.5 micrograms of MPP+ rat) showed 50% mortality; (2) The ICV administration of MPP+ produced a decrease in dopamine (DA) concentration in different areas of rat CNS studied: striatum (83%), hypophysis (95%) and median eminence (70%). However, olfactory bulb and substantia nigra were not affected; (3) MPP+ by ICV administration produced neurotoxic effect on the dopaminergic system. We also studied the possible protective action of acetyl-L-carnitine (ALC) against the neurotoxic action of MPP+. Rats were intraperitoneally injected daily for 8 days with 100 mg kg-1 of ALC and 3 days from the beginning of the MPP+ treatment; (4) We found that the ALC treatment significantly protected against mortality produced by the ICV injection of MPP+. Rats treated with ALC showed no mortality; (5) We did not find a protective effect on the dopaminergic system studying either catecholamine concentration or measuring tyrosine hydroxylase, neurofilament or glial fibrillary acid protein; (6) The results suggest that the ALC protective action could be related to energy metabolism.
Steffen
V
V
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Santiago
M
M
de la Cruz
C P
CP
Revilla
E
E
Machado
A
A
Cano
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage / Q000378:metabolism; D000108:Acetylcarnitine / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D015259:Dopamine Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007382:Intermediate Filaments / Q000187:drug effects; D020267:MPTP Poisoning; D008297:Male; D008473:Median Eminence / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects
D015259:Dopamine Agents; D018697:Nootropic Agents; D000108:Acetylcarnitine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine