Inhibition of hippocampal Jun N-terminal kinase enhances short-term memory but blocks long-term memory formation and retrieval of an inhibitory avoidance task.

Learning initiates a series of plastic events the occurrence of which are required for the storage of information related to the training experience. Several lines of evidence indicate that, in the rat hippocampus, different members of the family of mitogen-activated protein kinases (MAPK) play a key role in the onset of such plastic events. Using SP600125, the newly developed inhibitor of the MAPK c-Jun amino-terminal kinase (JNK), we show a direct involvement of this protein kinase in mnemonic processes. The intra-CA1 infusion of SP600125, at a dose that in naïve animals significantly reduced the phosphorylation levels of c-Jun without affecting the activity of ERK1/2 or p38 MAPK, enhanced short-term memory (STM) but blocked long-term memory (LTM) formation and retrieval of an inhibitory avoidance learning task. No action of this drug on locomotor/exploratory activity or general anxiety state could be detected. The significance of these results is discussed in the context of others describing the independence of LTM from STM.