MPTP-induced deficits in motor activity: neuroprotective effects of the spintrapping agent, alpha-phenyl-tert-butyl-nitrone (PBN).
In Experiment 1, groups of mice were administered either saline or MPTP (2 x 30 mg/kg, s.c., separated by a 24-hr interval) 30 min after being injected either PBN (15, 50 or 150 mg/kg, s.c., low, medium and high doses, respectively) or L-Deprenyl (0.25 or 10.0 mg/kg, s.c., low and high doses, respectively), the reference compound used, or saline. Tests of spontaneous motor activity 14 days later indicated that the MPTP-induced hypokinesia for locomotion and rearing was alleviated by prior administration with PBN (50 or 150 mg/kg) or L-Deprenyl (10.0 mg/kg); lower doses of PBN (15 mg/kg) and L-Deprenyl (0.25 mg/kg) did not affect the MPTP-induced deficits. Dopamine (DA) concentrations in the striatum confirmed a more severe loss of DA in the MPTP, PBN (15) + MPTP and Deprenyl(0.25) + MPTP groups than in the control group. Significant protection of DA was observed in the PBN(50) + MPTP, PBN(150) + MPTP and Deprenyl(10) + MPTP groups that did not exhibit an hypokinetic behaviour. In Experiment 2, the effects of repeated treatment with PBN (50 mg/kg, s.c. over 12 days), post-MPTP, were studied in aged (15-month-old) and young (3-month-old) mice. Subchronic administration of PBN increased substantially the motor activity of old and young mice that had received MPTP. Aged control (saline) mice showed an activity deficit compared to young control mice; this deficit was abolished by repeated PBN treatment. The results suggest that moderate-to-high doses of PBN whether injected in a single dose prior to MPTP or subchronically following MPTP injections may afford protective effects against both the functional changes and DA-loss caused by MPTP treatment, possibly through an antioxidant mechanism.
Fredriksson
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Department of Psychiatry, University of Uppsala, Sweden.
Eriksson
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Archer
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D003497:Cyclic N-Oxides; D004298:Dopamine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018476:Hypokinesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D019097:Spin Trapping
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D012642:Selegiline; C029217:phenyl-N-tert-butylnitrone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine