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Titolo:
Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice
Autore:
Fredriksson, A; Danysz, W; Quack, G; Archer, T;
Indirizzi:
Univ Gothenburg, Dept Psychol, SE-40530 Gothenburg, Sweden Univ Gothenburg Gothenburg Sweden SE-40530 , SE-40530 Gothenburg, Sweden Merz & Co, Dept Pharmacol Res, Frankfurt, Germany Merz & Co Frankfurt Germany Co, Dept Pharmacol Res, Frankfurt, Germany Uppsala Univ, Dept Neurosci, Psychiat Ulleraker, Uppsala, Sweden Uppsala Univ Uppsala Sweden urosci, Psychiat Ulleraker, Uppsala, Sweden
Titolo Testata:
JOURNAL OF NEURAL TRANSMISSION
fascicolo: 2, volume: 108, anno: 2001,
pagine: 167 - 187
SICI:
0300-9564(2001)108:2<167:COMAAW>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA RECEPTOR ANTAGONIST; MONOAMINE-DEPLETED RATS; PARKINSONS-DISEASE; REMACEMIDE HYDROCHLORIDE; SYNERGISTIC INTERACTIONS; PATCH-CLAMP; FLUCTUATIONS; LEVODOPA; AGONISTS; POTENTIATE;
Keywords:
MPTP; hypokinesia; locomotion, rearing, memantine, amantadine, MK-801, acute, chronic, L-Dopa; 5 mg/kg-20 mg/mg, co-administration, motor fluctuations, synergism; restoration, C57BL/6 mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Fredriksson, A Univ Gothenburg, Dept Psychol, Box 500, SE-40530 Gothenburg, Sweden Univ Gothenburg Box 500 Gothenburg Sweden SE-40530 Sweden
Citazione:
A. Fredriksson et al., "Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice", J NEURAL TR, 108(2), 2001, pp. 167-187

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 theformer 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 (5mg/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 (30 mg/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 0.3mg/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 MPTP-treated mice, whereas amantadine (3 and 10 mg/kg) restored both locomotor (30 mg/kg significantly increased locomotion but did not restore the activity level) and rearing (3mg/kg only) activity. MK-801 (0.1 and 0.3 mg/kg, s.c.) also increased significantly locomotor activity of L-Dopa-tolerant MPTP mice although the antikinetic action was not reversed, thereby precluding a restorative effect ofthe compound. These results, demonstrating both a synergistic and a restorative effect of the NMDA antagonists in coadministration with L-Dopa, demonstrate a putative antiparkinson action by these compounds in a functional animal model that incorporates the "wearing-off" complications of L-Dopa administration in the disorder.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/02/20 alle ore 11:39:01