REDUCED DORSAL HIPPOCAMPAL GLUTAMATE RELEASE SIGNIFICANTLY CORRELATESWITH THE SPATIAL MEMORY DEFICITS PRODUCED BY BENZODIAZEPINES AND ETHANOL

Memory deficits frequently occur after taking benzodiazepines and etha nol. We studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and et hanol in rats as an animal model of amnesia. These drugs potently impa ired spatial memory formation as evaluated by the Morris water maze ta sk, the rank order among tested treatments being the combination of tr iazolam (20 mu g/kg) with ethanol (2 g/kg)greater than or equal to tri azolam (100 mu g/kg)>ethanol (2 g/kg)greater than or equal to triazola m (20 mu g/kg)>rilmazafone (20 mu g/kg). On the other hand, these drug treatments also reduced glutamate release in the dorsal hippocampus b ut not in the cerebellum measured by microdialysis: the combined admin istration of triazolam with ethanol potently inhibited glutamate relea se to 60% of basal output in the dorsal hippocampus. These decreases i n hippocampal glutamate transmission closely correlated with the exten t of impairment of spatial memory performance (r=0.990). Thus, the pre sent results strongly indicated that presynaptic dysfunction in dorsal hippocampal glutamatergic neurons would be critical for spatial memor y deficits induced by benzodiazepines and ethanol. (C) 1998 IBRO. Publ ished by Elsevier Science Ltd.