Preservation of autoreceptor-mediated increases in dopamine synthesis in aged mice with experimentally-induced parkinsonism.
This study examined autoreceptor (i.e haloperidol)-mediated regulation of dopamine synthesis in normal aged mice and aged mice with a partial lesion of the nigrostriatal dopamine system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). There were no significant differences between haloperidol-induced increases in striatal dihydroxyphenylalanine (DOPA) accumulation between lesioned and unlesioned animals. Striatal DOPA/dopamine ratios were significantly increased in lesioned animals treated with haloperidol as compared to normal lesioned animals treated only with haloperidol. These data suggest that striatal dopamine synthetic capacity and autoreceptor-mediated regulation of dopamine synthesis are relatively preserved in aged mice, even after a moderate nigrostriatal lesion. Aged dopamine neurons appear to retain the ability to increase synthesis and release of dopamine in the presence of an appropriate pharmacological stimulus.
Schneider
J S
JS
Department of Neurobiology and Anatomy, Allegheny University of the Health Sciences, MCP Hahnemann University, Philadelphia, PA 19102, USA.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D017660:Autoreceptors / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000201:enzymology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D017660:Autoreceptors; D018492:Dopamine Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine