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 mechan isms involved in certain forms of learning and memory. We have previou sly demonstrated that the posttraining infusion of 6-cyano-7-nitroquin oxaline-2,3-dione, an lpha-amino-3-hydroxy-5-methylisoxazole-4-propion ic acid (AMPA) receptor blocker, into the dorsal hippocampus of rats, causes retrograde amnesia of an inhibitory avoidance training. Here, w e report on the effect of this learning task on (3)[H]AMPA binding to frozen rat brain sections. By using a quantitative autoradiographic an alysis, 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 subregion s of the hippocampal formation of rats trained in a step-down inhibito ry avoidance paradigm, compared to naive, shocked, and free exploratio n controls. This effect was evident between 30 and 180 min after train ing, and it was mainly due to an increase in the density, but not in t he affinity of binding sites. No alterations in (3)[H]AMPA binding wer e observed either in those animals that received only the footshock (s hocked group) or in animals that were submitted to 1 min of free explo ration of the training box (free exploration group). In the rest of th e brain regions, including the frontal cortex, entorhinal cortex, stri atum, amygdala, cerebellum, and thalamus, the (3)[H]AMPA binding remai ned unchanged. In addition, the binding of (3)[H]muscimol and (3)[H]fl unitrazepam to the GABA(A)/benzodiazepine receptor complex was unalter ed 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 rec eptors are involved in the neural mechanisms underlying certain forms of learning and memory. (C) 1995 Academic Press, Inc.