Behavioral and biochemical changes following acute administration of MPTP and MPP+.
The acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on mouse locomotor activity and striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were investigated. A single dose of either MPTP (10-30 mg/kg, i.p.) or MPP+ (5-20 ug/mouse, i.c.v.) decreased locomotor activity 10-40 min after injection: this locomotor effect was significantly suppressed by either pretreatment with nomifensine or 1-deprenyl alone, or by the combination of desmethylimipramine and 6-hydroxydopamine. Pretreatment with clorgyline did not suppress this behavior and a single dose of haloperidol enhanced the effect. The striatal levels of DA, 3-methoxytyramine and 5-HT increased in parallel with the decrease in locomotor activity caused by MPTP or MPP+. In contrast, levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were decreased by injection of either MPTP or MPP+. Possible mechanism(s) of the behavioral and biochemical changes caused by the acute actions of MPTP and MPP+ with respect to their neurotoxic effects on the nigrostriatal DA system are discussed.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000032:analysis*; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009627:Nomifensine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis*
D011725:Pyridines; D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D012642:Selegiline; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C001746:3-methoxytyramine; D015655:1-Methyl-4-phenylpyridinium; D003891:Desipramine; D004298:Dopamine; D006719:Homovanillic Acid