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Titolo:
Modifications of the behavioral profile of non-competitive NMDA receptor antagonists, memantine, amantadine and (+)MK-801 after chronic administration
Autore:
Hesselink, MB; Smolders, H; De Boer, AG; Breimer, DD; Danysz, W;
Indirizzi:
Merz & Co, Dept Pharmacol Res, D-60318 Frankfurt, Germany Merz & Co Frankfurt Germany D-60318 acol Res, D-60318 Frankfurt, Germany Leidendsmsterdam Ctr Drug Res, Dept Pharmacol, NL-2300 RA Leiden, Netherlan Leiden Amsterdam Ctr Drug Res Leiden Netherlands NL-2300 RA n, Netherlan
Titolo Testata:
BEHAVIOURAL PHARMACOLOGY
fascicolo: 1, volume: 10, anno: 1999,
pagine: 85 - 98
SICI:
0955-8810(199902)10:1<85:MOTBPO>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXCITATORY AMINO-ACIDS; GLUTAMATE ANTAGONISTS; DIZOCILPINE MK-801; QUINOLINIC ACID; RAT STRIATUM; SYNAPTIC PLASTICITY; PARKINSONS-DISEASE; DEPENDENCE; ASPARTATE; PHENCYCLIDINE;
Keywords:
NMDA receptor; amantadine; memantine; (+)MK-801; chronic treatment; ataxia; catalepsy; locomotor activation; learning impairment; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Danysz, W Merzrt,Co, Dept Pharmacol Res, Eckenheimer Landstr 100-104, D-60318 Frankfu Merz & Co Eckenheimer Landstr 100-104 Frankfurt Germany D-60318
Citazione:
M.B. Hesselink et al., "Modifications of the behavioral profile of non-competitive NMDA receptor antagonists, memantine, amantadine and (+)MK-801 after chronic administration", BEHAV PHARM, 10(1), 1999, pp. 85-98

Abstract

Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists show antiparkinsonian-like activity in animal models, and possess neuroprotective properties. However they also induce a number of behavioral side effects in rodents at higher doses; these include learning impairment, hyperlocomotion,and ataxia. The present study focused on the possible development of tolerance, or sensitization, to any of these effects after sustained administration, either by repeated injection or continuous infusion. When memantine or(+)MK-801 (20 and 0.31 mg/kg/day respectively) were either infused or repeatedly injected for 14 days, tolerance was observed to their learning impairing effect at high doses, in a passive avoidance test. Tolerance to their ataxic effect developed after repeated administration ((+)MK-801 and memantine), or after infusion (memantine). Sensitization to the locomotor stimulation was seen following repetitive injections of memantine for 14 days, butnot seen with (+)MK-801. In animals with an unilateral 6-OHDA lesion of the nigrostriatal system, acute administration of memantine caused ipsilateral rotations, which were augmented following 14 days of infusion. The potency of amantadine to antagonize neuroleptic-induced catalepsy was unchanged following either infusion or repeated injections. The various acute effects of non-competitive NMDA receptor antagonists were modified differently by sustained treatment (i.e. tolerance to learning impairment and ataxia; sensitization to memantine's locomotor stimulation). The anti-cataleptic activity of amantadine remained unaltered. However, differences between drugs and the two treatment regimens (i.e. repetitive versus continuous treatments) were apparent. (C) 1999 Lippincott Williams & Wilkins.

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Documento generato il 31/03/20 alle ore 09:46:28