ETHANOL WITHDRAWAL SEIZURES AND THE NMDA RECEPTOR COMPLEX

被引：397

作者：

GRANT, KA ^{[1
]}

VALVERIUS, P ^{[1
]}

HUDSPITH, M ^{[1
]}

TABAKOFF, B ^{[1
]}

机构：

[1] NIAAA,DIV INTRAMURAL CLIN & BIOL RES,PHYSIOL & PHARMACOL STUDIES LAB,ROCKVILLE,MD 20852

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1990年 / 176卷 / 03期

关键词：

(Mouse); Ca[!sup]2+[!/sup] channels; Ethanol dependence; MK-801; NMDA (N-methyl-D-aspartate); Withdrawal seizures;

D O I：

10.1016/0014-2999(90)90022-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Prior biochemical and electrophysiological studies have shown that low doses of ethanol inhibited calcium influx through the N-methyl-D-aspartate (NMDA) receptor/ionophore. The present data show that chronic ethanol treatment results in an increase in the number of NMDA receptor/ionophore complexes in the hippocampus, a brain area known to be associated with ethanol withdrawal seizure activity. Treatment during withdrawal with NMDA-exacerbated handling induced withdrawal seizures in the ethanol-dependent mice, while administration of the NMDA receptor-associated calcium channel antagonist MK-801 decreased the occurrence and severity of the withdrawal seizures in a dose-dependent manner. The results are consistent with the hypothesis that the up-regulation of the NMDA receptor systems following chronic ethanol treatment may mediate the seizures associated with ethanol withdrawal in dependent animals. © 1990.

引用

页码：289 / 296

页数：8

共 32 条

[1] ACUTE AND CHRONIC ETHANOL TREATMENTS ALTER GABA RECEPTOR-OPERATED CHLORIDE CHANNELS [J].

ALLAN, AM ;

HARRIS, RA .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1987, 27 (04) :665-670

[2] KINDLING AS A MODEL FOR ALCOHOL WITHDRAWAL SYNDROMES [J].

BALLENGER, JC ;

POST, RM .

BRITISH JOURNAL OF PSYCHIATRY, 1978, 133 (JUL) :1-14

[3] PHENCYCLIDINE INCREASES THE AFFINITY OF DIHYDROPYRIDINE CALCIUM-CHANNEL ANTAGONIST BINDING IN RAT-BRAIN [J].

BOLGER, GT ;

RAFFERTY, MF ;

SKOLNICK, P .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1985, 330 (03) :227-234

[4] ANTICONVULSANT ACTIVITY OF (+)-5-METHYL-10, 11-DIHYDRO-5H-DIBENZO[A,D]CYCLOHEPTEN-5, 10-IMINE (MK-801), A SUBSTANCE WITH POTENT ANTICONVULSANT, CENTRAL SYMPATHOMIMETIC, AND APPARENT ANXIOLYTIC PROPERTIES [J].

CLINESCHMIDT, BV ;

MARTIN, GE ;

BUNTING, PR .

DRUG DEVELOPMENT RESEARCH, 1982, 2 (02) :123-134

[5] INCREASED DIHYDROPYRIDINE-SENSITIVE CALCIUM CHANNELS IN RAT-BRAIN MAY UNDERLIE ETHANOL PHYSICAL-DEPENDENCE [J].

DOLIN, S ;

LITTLE, H ;

HUDSPITH, M ;

PAGONIS, C ;

LITTLETON, J .

NEUROPHARMACOLOGY, 1987, 26 (2-3) :275-279

[6] THE NOVEL ANTICONVULSANT MK-801 BINDS TO THE ACTIVATED STATE OF THE N-METHYL-D-ASPARTATE RECEPTOR IN RAT-BRAIN [J].

FOSTER, AC ;

WONG, EHF .

BRITISH JOURNAL OF PHARMACOLOGY, 1987, 91 (02) :403-409

[7] GLUTAMIC-ACID AND ETHANOL DEPENDENCE [J].

FREED, WJ ;

MICHAELIS, EK .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1978, 8 (05) :509-514

[8]

GOLDBERG MP, 1988, J PHARMACOL EXP THER, V245, P1081

[9]

GOLDSTEIN DB, 1972, J PHARMACOL EXP THER, V183, P14

[10] COMPARATIVE PHARMACOLOGY OF CALCIUM ANTAGONISTS - NIFEDIPINE, VERAPAMIL AND DILTIAZEM [J].

HENRY, PD .

AMERICAN JOURNAL OF CARDIOLOGY, 1980, 46 (06) :1047-1058

← 1 2 3 4 →