Recent evidence has shown that either intraventricular or intrahippocampal injection of the NMDA antagonist D-2-amino-5-phosphonovalerate (AP-5) produces a spatial learning deficit. This deficit is similar to that observed in aged animals. The spatial learning capacity of aged rats could, then, be related to changes in the status of hippocampal NMDA receptors. This study assessed hippocampal NMDA receptor binding in young and aged rats using the potent NMDA antagonist 3H [(±)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP). Initial characterization experiments indicated that 3H-CPP bound selectively to a class of receptors in hippocampal tissue with high affinity (39.5 nM). The 3H-CPP receptor binding capacity was significantly reduced in experimentally naive aged rats (24–25 months) as compared with young animals (5 months). A comparable reduction in 3H-CPP binding was found in a comparison of aged and young rats that had been trained on a spatial task in the Morris water maze. Furthermore, the reduction in 3H-CPP binding was correlated with the severity of the learning deficit present within the aged group. It was concluded that a reduction in hippocampal NMDA sites, as measured by 3H-CPP binding, may contribute to the emergence of cognitive deficits in aged animals.
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