Intra-septal injections of glucose and glibenclamide attenuate galanin-induced spontaneous alternation performance deficits in the rat.

Injection of the neuroactive peptide galanin into the rat hippocampus and medial septal area impairs spatial memory and cholinergic system activity. Conversely, injection of glucose into these same brain regions enhances spatial memory and cholinergic system activity. Glucose and galanin may both modulate neuronal activity via opposing actions at ATP-sensitive K+ (K-ATP) channels. The experiments described in this report tested the ability of glucose and the direct K-ATP channel blocker glibenclamide to attenuate galanin-induced impairments in spontaneous alternation performance in the rat. Intra-septal injection of galanin (2.5 microgram), 30 min prior to plus-maze spontaneous alternation performance, significantly decreased alternation scores compared to those of rats receiving injections of vehicle solution. Co-injection of glucose (20 nmol) or the K-ATP channel blocker glibenclamide (5 nmol) attenuated the galanin-induced performance deficits. Glibenclamide produced an inverted-U dose-response curve in its interaction with galanin, with doses of 0.5 and 10 nmol having no effect on galanin-induced spontaneous alternation deficits. Drug treatments did not alter motor activity, as measured by overall number of arm entries during spontaneous alternation testing, relative to vehicle injected controls. These findings support the hypothesis that, in the septal region, galanin and glucose act via K-ATP channels to modulate neural function and behavior.