Effect of PKC inhibitors and activators on memory

Changes in the activity of the enzyme protein kinase C (PKC) have been implicated in learning and memory consolidation, and in the induction of long-term potentiation. The precise role of PKC in memory processing is still unknown. Using 1-day-old chicks trained on a single-trial passive avoidance task, we demonstrate that inhibition of PKC activity by melittin induced retention loss, in a dose-dependent manner, in the second stage of a three-stage sequence of memory processing. The effect was lateralized to the left hemisphere of the chick forebrain. This effect of melittin was prevented by high concentrations (16-320 microM) of the PKC activator, phorbol 12-myristate 13-acetate (PMA). Furthermore, concentrations of PMA in the range 1.6 to 40 microM were shown to induce long-term memory consolidation following a weakly reinforced version of the learning task, which normally does not lead to formation of long-term memory. That these actions of PMA are attributable to PKC activation is supported by the further finding that the inactive phorbol ester 4 alpha-PDD had no effect either on melittin-induced amnesia or on memory consolidation following weakly reinforced learning. Paradoxically, concentrations of 16 microM or higher of PMA inhibited memory consolidation for the normal strongly reinforced learning trial, an effect again not observed with 40 alpha-PDD. The results are consistent with the view that PKC activity may be implicated in a pre-long-term stage of memory processing.