Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol.
Memory deficits frequently occur after taking benzodiazepines and ethanol. We studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and ethanol in rats as an animal model of amnesia. These drugs potently impaired spatial memory formation as evaluated by the Morris water maze task, the rank order among tested treatments being the combination of triazolam (20 micrograms/kg) with ethanol (2 g/kg) > or = triazolam (100 micrograms/kg) > ethanol (2 g/kg) > or = triazolam (20 micrograms/kg) > rilmazafone (20 micrograms/kg). On the other hand, these drug treatments also reduced glutamate release in the dorsal hippocampus but not in the cerebellum measured by microdialysis: the combined administration of triazolam with ethanol potently inhibited glutamate release to 60% of basal output in the dorsal hippocampus. These decreases in hippocampal glutamate transmission closely correlated with the extent of impairment of spatial memory performance (r = 0.990). Thus, the present results strongly indicated that presynaptic dysfunction in dorsal hippocampal glutamatergic neurons would be critical for spatial memory deficits induced by benzodiazepines and ethanol.
Shimizu
K
K
Department of Legal Medicine, Asahikawa Medical College, Japan.
Matsubara
K
K
Uezono
T
T
Kimura
K
K
Shiono
H
H
D000818:Animals; D001569:Benzodiazepines; D000431:Ethanol; D018698:Glutamic Acid / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D001569:Benzodiazepines; D000431:Ethanol; D018698:Glutamic Acid