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 h as been studied, using dopaminergic systems in the substantia nigra, s triatum, olfactory bulb, median eminence and hypophysis. The following results were obtained: (1) Rats with ICV administration of 1 mu l MPP (+) solution (62.5 mu g of MPP(+) rat) showed 50% mortality; (2) The I CV administration of MPP(+) produced a decrease in dopamine (DA) conce ntration in different areas of rat CNS studied: striatum (83%), hypoph ysis (95%) and median eminence (70%). However, olfactory bulb and subs tantia nigra were not affected; (3) MPP(+) by ICV administration produ ced neurotoxic effect on the dopaminergic system. We also studied the possible protective action of acetyl-L-carnitine (ALC) against the neu rotoxic action of MPP(+). Rats were intraperitoneally injected daily f or 8 days with 100 mg kg(-1) of ALC and 3 days from the beginning of t he 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 prote ctive effect on the dopaminergic system studying either catecholamine concentration or measuring tyrosine hydroxylase, neurofilament or glia l fibrillary acid protein; (6) The results suggest that the ALC protec tive action could be related to energy metabolism.