ATP-sensitive potassium channel blockade enhances spontaneous alternation performance in the rat: A potential mechanism for glucose-mediated memory enhancement

Peripheral and central injections of D-glucose enhance learning and memory in rats, and block memory impairments produced by morphine. The mechanism(s ) for these effects is (are) as yet unknown. One mechanism by which glucose might act on memory and other brain functions is by regulating the ATP-sen sitive potassium channel. This channel may couple glucose metabolism and ne uronal excitability, with channel blockade increasing the likelihood of sti mulus-evoked neurotransmitter release. The present experiments explored the effects of intra-septal injections of glucose and the ATP-sensitive potass ium channel blocker glibenclamide on spontaneous alternation behavior in th e rat. Intra-septal injections of glucose (20 nmol) or glibenclamide (10 nm ol), 30 min prior to plus-maze spontaneous alternation performance, signifi cantly enhanced alternation scores compared to rats receiving vehicle injec tions. Glibenclamide enhanced spontaneous alternation performance in an inv erted-U dose-response manner. Individually sub-effective doses of glucose ( 5 nmol:) and glibenclamide (5 nmol) significantly enhanced plus-maze altern ation scores when co-injected into the septal area. Glibenclamide (10 nmol) , when co-administered with morphine (4 nmol) 30 min prior to Y-maze sponta neous alternation performance, attenuated the performance-impairing effects of morphine alone. The present findings show that intra-septal injections of the: direct ATP-s ensitive potassium channel blocker glibenclamide, both alone and in conjunc tion with a sub-effective dose of glucose, enhance spontaneous alternation performance and attenuate the performance-impairing effects of morphine. Th e similarity of the results obtained with glibenclamide and glucose, togeth er with their similar actions on ATP-sensitive potassium channel function, suggests that glucose may modulate memory-dependent behavior in the rat by regulating the ATP-sensitive potassium channel. (C) 1999 IBRO. Published by Elsevier Science Ltd.