Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice

Journal of Neural Transmission
Anders FredrikssonTrevor Archer

Abstract

The antiparkinsonian effects of the uncompetitive NMDA antagonists, memantine, amantadine and MK-801, in combination with an acute subthreshold dose of L-Dopa (5 mg/kg) in drug-naive MPTP-treated mice or a suprathreshold dose (20 mg/kg) in L-Dopa tolerant MPTP-treated mice were investigated. In the former case, memantine (locomotion: 3 mg/kg; rearing: 1 mg/kg) and amantadine (locomotion and rearing: 10 mg/kg) injected 60 min before the subthreshold dose of L-Dopa (5 mg/kg), each induced an antiparkinsonian action in hypokinesic MPTP-treated mice that consisted of dose-specific, as opposed to dose-related, elevations of locomotion and rearing behaviour. At the same time, higher doses of memantine reduced further the rearing (10 and 30 mg/kg) and locomotor (30mg/kg) behaviour of the MPTP-treated mice. MK-801 plus L-Dopa elevated locomotion (0.1 mg/kg) but reduced rearing at the 0.3 mg/kg dose. In control, saline-treated mice, memantine (3, 10 and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour but decreased rearing behaviour, while amantadine produced no effects. Memantine increased locomotor (1 and 3 mg/kg, s.c.; 1 mg/kg dose restored activity) and rearing (0.3 and 3 mg/kg) activity in the L-Dopa tolerant ...Continue Reading

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Citations

Sep 29, 2009·Breast Cancer Research and Treatment·William G NorthLauna Lynch
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