Src kinase activity is required for avoidance memory formation and recall

Using 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-D]pyrimidine (PP2), a specific inhibitor of the Src family of tyrosine kinases, here we show a direct involvement of these enzymes in memory formation and recall. When infused into the CA1 region of the dorsal hippocampus, immediately or 30 min after training rats in a one-trial inhibitory avoidance task, PP2 but not its inactive analog 4-amino-7-phenylpyrazol[3,4-D]pyrimidine (PP3), blocked short- (STM) and long-term memory (LTM) formation, as tested 2 or 24 h post-training, respectively. PP2 had no effect on STM when given at 60 min post-training or on LTM when administered at 60, 120 or 180 min after the training session, but blocked memory recall when infused into CA1 15 min before a LTM expression test. Hence, activity of the Src family of tyrosine kinases is required in the CA1 region of the rat dorsal hippocampus for the normal formation and retrieval of one-trial inhibitory avoidance memory.