title: Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on retinal dopaminergic system in mice.
abstract: The neurotoxins methamphetamine (METH) and MPTP are well-known for their effects on the nigrostriatal dopaminergic system and use in modeling neurodegenerative disorders such as Parkinson's disease. It is not well-known though, how METH or MPTP affects the visual system and specifically the retinal dopaminergic system. This study was designed to examine acute effects of multiple doses of METH and MPTP on the retinal dopaminergic system. Mice were exposed to either low- (LD) 10 mg/kg total dose or high-dose (HD) 30 mg/kg total dose, of METH or MPTP and the retinal catecholaminergic system was analyzed by HPLC. METH produced no significant changes in dopamine (DA), its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) or DA usage in the retina. LD-MPTP produced no change in DA level, but significantly decreased DOPAC and HVA. LD-MPTP also significantly decreased DA usage as measured by the DOPAC/DA and HVA/DA ratios. HD-MPTP significantly decreased DA, DOPAC and HVA, but did not affect DA usage. Taken together these results suggest that inhibition of the DA metabolizing enzymes monoamine oxidase A (MAO) or catechol-O-methyl transferase (COMT) may take place at lower doses of MPTP treatment; conversely, higher doses of MPTP may cause decreases in DA, DOPAC and HVA through another mechanism.
authors.affiliation: Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/USFDA, Jefferson, AR 72079, USA.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Hamilton
authors.forename: William J
authors.initials: WJ
authors.lastname: Trickler
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Robinson
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D006719:Homovanillic Acid