Influence of potassium channel modulators on cognitive processes in mice.
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 microg per mouse i.c.v.), pinacidil (5-25 microg per mouse i.c.v.) and cromakalim (10-25 microg per mouse i.c.v.) immediately after the training session produced an amnesic effect. 3. Tetraethylammonium (TEA; 1-5 microg per mouse i.c.v.), apamin (10 ng per mouse i.c.v.), charybdotoxin (1 microg per mouse i.c.v.), gliquidone (3 microg per mouse i.c.v.) and glibenclamide (1 microg 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.
Ghelardini
C
C
Department of Preclinical and Clinical Pharmacology, Florence, Italy.
Galeotti
N
N
Bartolini
A
A
D000647:Amnesia / Q000517:prevention & control; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D018999:Charybdotoxin / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008914:Minoxidil / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects*; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D019806:Cromakalim; D018999:Charybdotoxin; D001030:Apamin; D008914:Minoxidil; D019789:Tetraethylammonium; D020110:Pinacidil; C010969:gliquidone; D005905:Glyburide