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Titolo:
DIZOCILPINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS OF LOW-AFFINITY UNCOMPETITIVE NMDA ANTAGONISTS
Autore:
GRANT KA; COLOMBO G; GRANT J; ROGAWSKI MA;
Indirizzi:
WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,MED CTRBLVD WINSTON SALEM NC 27157 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED WINSTON SALEM NC 27157 NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITAB SECT BETHESDA MD 20892
Titolo Testata:
Neuropharmacology
fascicolo: 12, volume: 35, anno: 1996,
pagine: 1709 - 1719
SICI:
0028-3908(1996)35:12<1709:DDSEOL>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE ANTAGONIST; RAT HIPPOCAMPAL-NEURONS; PHENCYCLIDINE-LIKE; 0,11-DIHYDRO-5H-DIBENZO)A,D>CYCLOHEPTEN-5,10-IMINE ADCI; ANTICONVULSANT REMACEMIDE; RECEPTOR ANTAGONISTS; PARKINSONS-DISEASE; CHANNEL BLOCKERS; BINDING-SITES; MK-801;
Keywords:
DIZOCILPINE (MK-801); DRUG DISCRIMINATION; GLUTAMATE RECEPTOR; KETAMINE; N-METHYL-D-ASPARTATE ANTAGONIST; N-METHYL-D-ASPARTATE RECEPTOR; PHENCYCLIDINE; RAT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
74
Recensione:
Indirizzi per estratti:
Citazione:
K.A. Grant et al., "DIZOCILPINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS OF LOW-AFFINITY UNCOMPETITIVE NMDA ANTAGONISTS", Neuropharmacology, 35(12), 1996, pp. 1709-1719

Abstract

The dizocilpine-like discriminative stimulus effects of a variety of channel blocking (uncompetitive) N-methyl-D-aspartate (NMDA) receptor antagonists were examined in rats trained to discriminate dizocilpine (0.17 mg/kg, i.p) from saline in a two-lever operant procedure. The dissociative anesthetic-type NMDA antagonists dizocilpine (ED(50) 0.05 mg/kg), phencyclidine (ED(50) 3.4 mg/kg) and ketamine (ED(50) 14 mg/kg)showed complete substitution without producing significant decreases in response rates, whereas dexoxadrol (ED(50) 4.3 mg/kg) also producedcomplete substitution with a concomitant decrease (35%) in response rate. Similarly, the low-affinity antagonist memantine resulted in complete substitution (ED(50) 9.7 mg/kg) at doses that significantly reduced (68%) the response rate. All other low-affinity antagonists resulted in either partial or no substitution for the discriminative stimuluseffects of dizocilpine at doses that significantly decreased average response rates. These include (ED(50) values in parentheses) remacemide (29 mg/kg), the remacemide metabolite 1,2-diphenyl-2-propylamine (ARL 12495) (14 mg/kg), phencylcyclopentylamine (25 mg/kg), dextromethorphan (46 mg/kg), ,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine (ADCI; no substitution) and levoxadrol (no substitution). We conclude that low-affinity uncompetitive NMDA antagonists have discriminative stimulus properties distinct from dissociative anesthetic-type uncompetitive NMDA antagonists. The lowest-affinity antagonists show virtually nosubstitution for dizocilpine, whereas the relatively more potent low-affinity antagonists (such as memantine) exhibit greater substitution,but complete substitution is obtained only at rate-reducing doses. (C) 1997 Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 03:32:47