Influence of potassium channel modulators on cognitive processes in mice

被引:43
作者
Gherardini, C [1 ]
Galeotti, N [1 ]
Bartolini, A [1 ]
机构
[1] Univ Florence, Dept Preclin & Clin Pharmacol, I-50134 Florence, Italy
关键词
potassium channel openers; potassium channel antagonists; learning and memory; minoxidil; pinacidil; cromakalim; sulphonylureas; apamin; charybdotoxin; tetraethylammonium;
D O I
10.1038/sj.bjp.0701709
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The effect of i.c.v. administration of different potassium channel openers (minoxidil, pinacidil, cromakalim) and potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone, glibenclamide) on memory processes was evaluated in the mouse passive avoidance test. 2 The administration of minoxidil (10 mu g per mouse i.c.v.), pinacidil (5-25 mu g per mouse i.c.v.) and cromakalim (10-25 mu g per mouse i.c.v.) immediately after the training session produced an amnesic effect. 3 Tetraethylammonium (TEA; 1-5 mu g per mouse i.c.v.), apamin (10 ng per mouse i.c.v.), charybdotoxin (1 mu g per mouse i.c.v.), gliquidone (3 pg per mouse i.c.v.) and glibenclamide (1 mu g per mouse i.c.v.), administered 20 min before the training session, prevented the potassium channel opener-induced amnesia. 4 At the highest effective doses, none of the drugs impaired motor coordination, as revealed by the rota rod test, or modified spontaneous motility and inspection activity, as revealed by the hole board test. 5 These results suggest that the modulation of potassium channels plays an important role in the regulation of memory processes. On this basis, the potassium channel blockers could be useful in the treatment of cognitive deficits.
引用
收藏
页码:1079 / 1084
页数:6
相关论文
共 25 条
[1]   PRIMARY CHANGES OF MEMBRANE CURRENTS DURING RETENTION OF ASSOCIATIVE LEARNING [J].
ALKON, DL ;
LEDERHENDLER, I ;
SHOUKIMAS, JJ .
SCIENCE, 1982, 215 (4533) :693-695
[2]   POTASSIUM CHANNELS IN NERVOUS-TISSUE [J].
ARONSON, JK .
BIOCHEMICAL PHARMACOLOGY, 1992, 43 (01) :11-14
[3]  
Boakye M., 1994, Society for Neuroscience Abstracts, V20, P1673
[4]   Molecular and functional diversity of K+ channels [J].
Christie, MJ .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 1995, 22 (12) :944-951
[6]  
COOK NS, 1990, POTASSIUM CHANNELS S, P181
[7]   Effect of apamin, a selective blocker of Ca2+-activated K+-channel, on habituation and passive avoidance responses in rats [J].
Deschaux, O ;
Bizot, JC .
NEUROSCIENCE LETTERS, 1997, 227 (01) :57-60
[8]   Apamin improves learning in an object recognition task in rats [J].
Deschaux, O ;
Bizot, JC ;
Goyffron, M .
NEUROSCIENCE LETTERS, 1997, 222 (03) :159-162
[9]  
EDWARDS G, 1993, ANNU REV PHARMACOL, V33, P597, DOI 10.1146/annurev.pharmtox.33.1.597
[10]   POTASSIUM CHANNEL DYSFUNCTION IN FIBROBLASTS IDENTIFIES PATIENTS WITH ALZHEIMER-DISEASE [J].
ETCHEBERRIGARAY, R ;
ITO, E ;
OKA, K ;
TOFELGREHL, B ;
GIBSON, GE ;
ALKON, DL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :8209-8213