Intrahippocampal Wortmannin Infusion Enhances Long-Term Spatial and Contextual Memories

The transition from short- to long-term memory involves several biochemical cascades, some of which act in an antagonistic manner. Post-training intrahippocampal administration of wortmannin, a pharmacological inhibitor of phosphatidylinositol 3-kinase, had no effect on memory tested 3 h later, but improved long-term memory tested 48 h following the completion of training. This effect was seen in two hippocampus-dependent tasks: the Morris water maze, using both massed and distributed training paradigms, and contextual fear conditioning. The improvement of long-term memory appears to be the result of enhanced consolidation, as wortmannin had no effect on memory recall. These results are consistent with the hypothesis that memory consolidation involves competing processes, and that blockade of an inhibitory constraint facilitates the consolidation process.