Further evidence for the involvement of a hippocampal cGMP/cGMP-dependent protein kinase cascade in memory consolidation.

Hippocampal cyclic GMP (cGMP) has been recently postulated to participate in an early phase of memory consolidation of an inhibitory avoidance learning in rats. Here we report on the effects of the intrahippocampal infusion of a soluble guanylyl cyclase inhibitor (LY 83583) in the consolidation of one-trial step-down inhibitory avoidance and on the effect of this task on hippocampal cGMP levels and cGMP-dependent protein kinase (PKG) activity. Bilateral intrahippocampal administration of LY 83583 (2.5 micrograms per side) caused full amnesia for inhibitory avoidance when given immediately (0 min) after training, but not 30 min post-training. Rats submitted to the inhibitory avoidance task showed a significant increase in both cGMP levels and in PKG activity in the hippocampus at 0 min after training. No changes were observed 30 min after training. These findings provide further evidence that the hippocampal cGMP/PKG cascade is involved in the early stages of memory formation of an inhibitory avoidance task in rats.