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Titolo:
Effects of a novel uncompetitive NMDA receptor antagonist, MRZ 2/579 on ethanol self-administration and ethanol withdrawal seizures in the rat
Autore:
Bienkowski, P; Krzascik, P; Koros, E; Kostowski, W; Scinska, A; Danysz, W;
Indirizzi:
Inst Psychiat & Neurol, Dept Pharmacol & Physiol Nervous Syst, PL-02957 Warsaw, Poland Inst Psychiat & Neurol Warsaw Poland PL-02957 t, PL-02957 Warsaw, Poland Med Acad Warsaw, Dept Expt & Clin Pharmacol, Warsaw, Poland Med Acad Warsaw Warsaw Poland ept Expt & Clin Pharmacol, Warsaw, Poland Med Acad Warsaw, Fac Dent, Dept Otolaryngol, Warsaw, Poland Med Acad Warsaw Warsaw Poland ac Dent, Dept Otolaryngol, Warsaw, Poland Merz & Co, Dept Pharmacol Res, Frankfurt, Germany Merz & Co Frankfurt Germany Co, Dept Pharmacol Res, Frankfurt, Germany
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 413, anno: 2001,
pagine: 81 - 89
SICI:
0014-2999(20010209)413:1<81:EOANUN>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO CHARACTERIZATION; D-ASPARTATE ANTAGONISTS; AMINO-ACID ANTAGONISTS; CHANNEL BLOCKERS; INDUCED NEUROTOXICITY; REINFORCED BEHAVIOR; GLUTAMATE; MEMANTINE; MK-801; MICE;
Keywords:
ethanol self-administration; ethanol withdrawal; NMDA receptor antagonist; MRZ 2/579; (rat);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Bienkowski, P Inst Psychiat & Neurol, Dept Pharmacol & Physiol Nervous Syst, Al Sobieskiego 1-9, PL-02957 Warsaw, Poland Inst Psychiat & Neurol Al Sobieskiego 1-9 Warsaw Poland PL-02957
Citazione:
P. Bienkowski et al., "Effects of a novel uncompetitive NMDA receptor antagonist, MRZ 2/579 on ethanol self-administration and ethanol withdrawal seizures in the rat", EUR J PHARM, 413(1), 2001, pp. 81-89

Abstract

It has been repeatedly reported that NMDA receptors may contribute to ethanol-induced discriminative stimulus effects and withdrawal syndrome, However, the role of NMDA receptors in the reinforcing properties of ethanol remains unclear. The aim of the present study was to evaluate effects of the novel low-affinity, uncompetitive NMDA receptor antagonist. 1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride (MRZ 2/579), on ethanol self-administration and ethanol withdrawal-associated seizures in rats. Both an operant(lever pressing for ethanol) and non-operant two-bottle choice setups wereemployed to initiate ethanol self-administration. In another procedure. forced treatment with high doses (9-15 g/kg/day) was used to induce physical dependence on ethanol. MRZ 2/579 delivered chronically by osmotic minipumps(9.6 mg/day, s.c.) did not alter either operant or non-operant ethanol drinking behaviour in a maintenance phase of ethanol self-administration. In contrast, repeated daily injections of the drug (5 mg/kg, i.p.) led to a progressive decrease in operant responding for ethanol. MRZ 2/579 (0.5-7.5 mg/kg, i.p.) and another low-affinity NMDA receptor antagonist, memantine(1-10mg/kg, i.p.) dose-dependently suppressed ethanol withdrawal seizures with efficacies comparable with that of a standard benzodiazepine derivative, diazepam. The results of the present study indicate that: (i) intermittent administration of MRZ 2/579 may lead to a gradual decrease of operant responding for ethanol: and (ii) the group of low-affinity uncompetitive NMDA receptor antagonists may be an interesting alternative to benzodiazepines in the treatment of alcohol withdrawal. (C) 2001 Elsevier science B.V. All rights reserved.

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Documento generato il 28/01/20 alle ore 15:29:06