LEARNING-SPECIFIC, TIME-DEPENDENT INCREASE IN [H-3] PHORBOL DIBUTYRATE BINDING TO PROTEIN-KINASE-C IN SELECTED REGIONS OF THE RAT-BRAIN

Several lines of evidence indicate that protein kinase C (PKC) participates in long-term potentiation (LTP) and in certain forms of learning. Here we describe a rapid, specific and time-dependent increase in [H-3]phorbol-12,13-dibutyrate ([H-3]PDBu) binding to membrane-associated PKC in selected brain regions of rats submitted to an inhibitory avoidance task. A quantitative film autoradiographic method was used to determine the amount and distribution of membrane-bound PKC in rats sacrificed at various time intervals after training. At 0, 30 and 120 min following training there was a prominent increase (up to 200%) in the binding of [H-3]PDBu throughout the hippocampus relative to naive, shocked or habituated control groups. No significant changes in [H-3]PDBu binding in any brain region were found at 180 min after training. Similar training-specific increments in the binding of [H-3]PDBu were observed in the frontal, parietal and entorhinal cerebral cortices, amygdala and cerebellum. The maximal effect was seen at 30 min in the CA(2) region of the hippocampus (+200%) and at 30 and 120 min after training in the amygdala (+170%) in comparison to naive control values. No alterations in [H-3]PDBu binding were found in the other brain regions studied. The present findings, together with previous data reporting a similar temporal course in the effects of intrahippocampal or intraamygdala infusion of specific PKC inhibitors on memory, suggest that PKC activation plays a role in the acquisition and consolidation of an inhibitory avoidance learning.