Inhibitory avoidance training induces rapid and selective changes in 3[H]AMPA receptor binding in the rat hippocampal formation.

The AMPA receptor has been shown to participate in the synaptic mechanisms involved in certain forms of learning and memory. We have previously demonstrated that the posttraining infusion of 6-cyano-7-nitroquinoxaline-2,3-dione, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor blocker, into the dorsal hippocampus of rats, causes retrograde amnesia of an inhibitory avoidance training. Here, we report on the effect of this learning task on 3[H]AMPA binding to frozen rat brain sections. By using a quantitative autoradiographic analysis, we were able to demonstrate that the binding of 3[H]-AMPA was increased by 40-80% in the CA1, CA2, CA3, and dentate gyrus subregions of the hippocampal formation of rats trained in a step-down inhibitory avoidance paradigm, compared to naive, shocked, and free exploration controls. This effect was evident between 30 and 180 min after training, and it was mainly due to an increase in the density, but not in the affinity of binding sites. No alterations in 3[H]AMPA binding were observed either in those animals that received only the footshock (shocked group) or in animals that were submitted to 1 min of free exploration of the training box (free exploration group). In the rest of the brain regions, including the frontal cortex, entorhinal cortex, striatum, amygdala, cerebellum, and thalamus, the 3[H]AMPA binding remained unchanged. In addition, the binding of 3[H]muscimol and 3[H]-flunitrazepam to the GABAA/benzodiazepine receptor complex was unaltered in all the experimental groups. In conclusion, rats submitted to a one-trial inhibitory avoidance training showed a rapid, selective, and specific increase in 3[H]AMPA binding in the hippocampal formation. The present findings support the hypothesis that hippocampal AMPA receptors are involved in the neural mechanisms underlying certain forms of learning and memory.