Release of dopamine by perfusion with 1-methyl-4-phenylpyridinium ion (MPP +) into the striatum is associated with hydroxyl free radical generation

• Published in: Brain research Vol. 906; no. 1; pp. 170 - 175
• Main Authors: Obata, Toshio, Yamanaka, Yasumitsu, Kinemuchi, Hiroyasu, Oreland, Lars
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 06-07-2001; Amsterdam Elsevier; New York, NY
• Subjects: 1-Methyl-4-phenylpyridinium - toxicity; 1-Methyl-4-phenylpyridinium ion (MPP +); Adrenergic Uptake Inhibitors - pharmacology; Animals; Antifungal Agents - pharmacology; Biological and medical sciences; Cell Membrane - drug effects; Cell Membrane - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine - metabolism; Dopamine - pharmacology; Dose-Response Relationship, Drug; Drug Interactions - physiology; Extracellular Space - drug effects; Extracellular Space - metabolism; Herbicides - toxicity; Hydroxybenzoates - metabolism; Hydroxyl radical; Hydroxyl Radical - metabolism; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Male; Medical sciences; Neostriatum - drug effects; Neostriatum - metabolism; Neostriatum - physiopathology; Nerve Degeneration - chemically induced; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neural Pathways - drug effects; Neural Pathways - metabolism; Neural Pathways - physiopathology; Neurology; Neurons - drug effects; Neurons - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Parkinson’s disease; Rats; Rats, Wistar; Reserpine; Reserpine - pharmacology; Salicylic Acid - pharmacology; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - physiopathology; Disorders of the nervous system; Dopamine; 1-Methyl-4-phenylpyridinium ion (MPP +); Hydroxyl radical; Reserpine; Parkinson’s disease; Nervous system diseases; Rat; Rodentia; Central nervous system; Parkinson disease; Basal ganglion; Corpus striatum; Catecholamine; Free radical; Cerebral disorder; Toxin; Vertebrata; Mammalia; Cell death; Animal; Central nervous system disease; Neurotoxin; Neurotransmitter; Degenerative disease; Release; Brain (vertebrata); Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02238-7

In Parkinson’s disease (PD), the dopamine (DA) neuronal cell death in the nigrostriatal system has been proposed to be mediated by reactive oxygen radicals such as hydroxyl radicals (
·OH). This
·OH production may cause lipid peroxidation of cell membranes leading to neuronal cell death. This paper report that the DA-selective neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP
+), (1 nmol/μl per min for 1 h) infusion into the striatum of rats induces elevation of extracellular DA and
·OH formation. These elevations seem to induce lipid peroxidation of striatum membranes, as detected by increases in non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) levels. To test the involvement of DA release in the
·OH generation and lipid peroxidation, the rats were pretreated with reserpine (5 mg/kg, i.v., 24 h before MPP
+ or without MPP
+) to deplete presynaptic DA. Reserpine treatment alone did not change the levels of DA or 2,3-DHBA, while the combined treatment with both MPP
+ and reserpine clearly decreased 2,3-DHBA, as well as DA levels, compared to those in the group treated with MPP
+ alone. After injection into reserpinized rats, DA at various doses (2, 5 and 10 μM) small increased 2,3-DHBA levels dose-dependently, as compared to the MPP
+ alone-treated group. These results clearly indicate that MPP
+ perfusion into the striatum increases extracellular DA levels and this increase may concomitantly induce the formation of reactive free oxygen radicals, such as
·OH free radicals. These events may contribute, at least in part, to the nigrostriatal neurons cell death after MPP
+.