FACILITATION OF GLUTAMATE RECEPTORS ENHANCES MEMORY

A benzamide drug that crosses the blood-brain barrier and facilitates lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) recepto r-mediated synaptic responses was tested for its effects on memory in three behavioral tasks. The compound reversibly increased the amplitud e and prolonged the duration of field excitatory postsynaptic potentia ls in hippocampal slices and produced comparable effects in the dentat e gyrus in situ after intraperitoneal injections, Rats injected with t he drug 30 min prior to being given a suboptimal number of training tr ials in a two-odor discrimination task were more likely than controls to select the correct odor in a retention test carried out 96 hr later . Evidence for improved memory was also obtained in a water maze task in which rats were given only four trials to find a submerged platform in the presence of spatial cues; animals injected with the drug 30 mi n before the training session were significantly faster than vehicle-i njected controls in returning to the platform location when tested 24 hr after training. Finally, the drug produced positive effects in a ra dial maze test of short-term memory. Well trained rats were allowed to retrieve rewards from four arms of an eight arm maze and then tested for reentry errors 8 hr later. The number of such errors was substanti ally reduced on days in which the animals were injected with the drug before initial learning. These results indicate that a drug that facil itates glutamatergic transmission enhances the encoding of memory acro ss tasks involving different sensory cues and performance requirements . This may reflect an action on the cellular mechanisms responsible fo r producing synaptic changes since facilitation of AMPA receptors prom otes the induction of the long-term potentiation effect.