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-sensitive potassium channel. This channel may couple glucose metabolism and neuronal excitability, with channel blockade increasing the likelihood of stimulus-evoked neurotransmitter release. The present experiments explored the effects of intra-septal injections of glucose and the ATP-sensitive potassium channel blocker glibenclamide on spontaneous alternation behavior in the rat. Intra-septal injections of glucose (20 nmol) or glibenclamide (10 nmol), 30 min prior to plus-maze spontaneous alternation performance, significantly enhanced alternation scores compared to rats receiving vehicle injections. Glibenclamide enhanced spontaneous alternation performance in an inverted-U dose-response manner. Individually sub-effective doses of glucose (5 nmol:) and glibenclamide (5 nmol) significantly enhanced plus-maze alternation scores when co-injected into the septal area. Glibenclamide (10 nmol), when co-administered with morphine (4 nmol) 30 min prior to Y-maze spontaneous alternation performance, attenuated the performance-impairing effects of morphine alone. The present findings show that intra-septal injections of the: direct ATP-sensitive potassium channel blocker glibenclamide, both alone and in conjunction with a sub-effective dose of glucose, enhance spontaneous alternation performance and attenuate the performance-impairing effects of morphine. The similarity of the results obtained with glibenclamide and glucose, together 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.