The Journal of Neuroscience, January 15, 2001, 21(2):609-614
Intrahippocampal Infusions of K-ATP Channel Modulators Influence
Spontaneous Alternation Performance: Relationships to Acetylcholine
Release in the Hippocampus
Mark R.
Stefani1 and
Paul E.
Gold2
1 Department of Psychiatry, Yale University School of
Medicine, Veterans Affairs Medical Center, West Haven, Connecticut
06516, and 2 Department of Psychology, University of
Illinois at Urbana-Champaign, Champaign, Illinois 61820
One mechanism by which administration of glucose enhances cognitive
functions may be by modulating central ATP-sensitive potassium (K-ATP)
channels. K-ATP channels appear to couple glucose metabolism and
neuronal excitability, with channel blockade increasing the likelihood
of neurosecretion. The present experiment examined the effects of
glucose and the direct K-ATP channel modulators glibenclamide and
lemakalim on spontaneous alternation performance and hippocampal ACh
release. Rats received either artificial CSF vehicle or vehicle
plus drug for two consecutive 12 min periods via microdialysis
probes (3 mm; flow rate of 2.1 µl/min) implanted in the left
hippocampus. During the second 12 min period, rats were tested for
spontaneous alternation performance. Dialysate was simultaneously
collected for later analysis of ACh content. Both glucose (6.6 mM) and glibenclamide (100 µM) significantly increased alternation scores compared with those of controls. Conversely, lemakalim (200 µM) significantly reduced
alternation scores relative to those of controls. Simultaneous
administration of lemakalim with either glucose or glibenclamide
resulted in alternation scores not significantly different from control
values. All drug treatments enhanced hippocampal ACh output relative to control values. The results demonstrate that K-ATP channel modulators influence behavior when administered directly into the hippocampus, with channel blockers enhancing and openers impairing spontaneous alternation performance, thus supporting the hypothesis that glucose enhances memory via action at central K-ATP channels. That lemakalim, as well as glibenclamide and glucose, increased hippocampal ACh output
suggests a dissociation between the effects of K-ATP channel modulators
on behavior and hippocampal ACh release.
Key words:
memory; K-ATP channels; spatial memory; glucose; glibenclamide; lemakalim; hippocampus; acetylcholine
Copyright © 2001 Society for Neuroscience 0270-6474/01/212609-06$05.00/0
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