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Titolo:
EVALUATION OF THE REINFORCING AND DISCRIMINATIVE STIMULUS PROPERTIES OF THE LOW-AFFINITY N-METHYL-D-ASPARTATE CHANNEL BLOCKER MEMANTINE
Autore:
NICHOLSON KL; JONES HE; BALSTER RL;
Indirizzi:
VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,BOX 980310 RICHMOND VA 23298 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOLRICHMOND VA 23298
Titolo Testata:
Behavioural pharmacology
fascicolo: 3, volume: 9, anno: 1998,
pagine: 231 - 243
SICI:
0955-8810(1998)9:3<231:EOTRAD>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
NMDA RECEPTOR ANTAGONISTS; PHENCYCLIDINE-LIKE; PARKINSONS-DISEASE; RHESUS-MONKEYS; PHARMACOLOGICAL SPECIFICITY; BEHAVIORAL PHARMACOLOGY; SQUIRREL-MONKEYS; RATS; GLUTAMATE; AMANTADINE;
Keywords:
AMANTADINE; DRUG DISCRIMINATION; MEMANTINE; MONKEY; NMDA RECEPTOR; PHENCYCLIDINE; RAT; SELF-ADMINISTRATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
K.L. Nicholson et al., "EVALUATION OF THE REINFORCING AND DISCRIMINATIVE STIMULUS PROPERTIES OF THE LOW-AFFINITY N-METHYL-D-ASPARTATE CHANNEL BLOCKER MEMANTINE", Behavioural pharmacology, 9(3), 1998, pp. 231-243

Abstract

Memantine (MEM) is currently in clinical use in Europe for the treatment of various neurological disorders. It is a low-affinity channel blocker of N-methyl-D-aspartate (NMDA) receptors whose voltage-dependent, rapid binding kinetics are believed to limit its phencyclidine (PCP)-like side effects. MEM, and its analog amantadine (AMA), which has also been demonstrated to have some NMDA antagonist activity, were evaluated for PCP-like behavioral effects. The discriminative stimulus properties of MEM and AMA were tested in monkeys and rats trained to discriminate PCP from saline using a standard two-lever drug discriminationparadigm under a fixed ratio (FR) schedule of food reinforcement. In rats, MEM resulted in a dose-dependent substitution for PCP; however, full substitution occurred only at response rate suppressing doses. AMA failed to substitute for PCP at any dose tested, For MEM, all four monkeys showed complete substitution for PCP at doses which did not greatly decrease rates of responding. Conversely, AMA occasioned little or no responding on the PCP-associated lever in any of the subjects. Intravenous self-administration of MEM and AMA was tested under a FR schedule of reinforcement in four monkeys trained to lever press for infusions of PCP, MEM served as a reinforcer in all subjects at one or more doses tested. For two of the subjects, at least one dose of AMA maintained rates of self-administration above those for saline. For both MEM and AMA, maximal response rates were considerably lower than with PCP self-administration and both drugs were much less potent in monkeysthan would be predicted from rodent studies. The data show that MEM shares discriminative stimulus effects with PCP under these testing conditions, whereas the chemically similar compound AMA does not. MEM also serves as a positive reinforcer in rhesus monkeys, whereas AMA can serve as a weak reinforcer in only some subjects. Both AMA and MEM are reported to function as NMDA antagonists, yet clear differences exist in their behavioral effects,vith MEM acting more like a PCP-like antagonist. In addition, despite the rapid channel kinetics of MEM's NMDA receptor blockade, it may have some PCP-like abuse potential in humans at doses above the normal therapeutic levels. Behav Pharmacol 1998; 9:231-243 (C) 1998 Lippincott-Raven Publishers.

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Documento generato il 30/11/20 alle ore 03:33:31