Investigations on the role of hippocampal protein kinase C on memory processes: pharmacological approach.

We report here investigations on the functional involvement of hippocampal protein kinase C (PKC) in learning and long-term retention of spatial discrimination in a radial maze. A pharmacological approach was employed to test the behavioural effects of intrahippocampal injections of drugs that either activate or inhibit PKC activity. Mice with intrahippocampal guide cannula were trained in a mixed spatial reference-working memory task during 7 daily sessions. Sixteen days later, the animals were submitted to a retention session. In the first experiment, the animals were treated before each learning session with polymyxin B (PMB, a PKC inhibitor) and their scores were compared to those of an appropriate control group. In the second experiment, a group received the injection of 1-oleoyl-2-acetyl glycerol (OAG, a PKC activator) before and after the 7th learning session in order to test the effect of activation of PKC on long-term retention. The results showed that: (1) PMB administration delayed the acquisition of the reference memory component of the task, whereas long-term retention appeared to be improved; and (2) administration of OAG at the end of the acquisition phase improved long-term retention. Neither PMB nor OAG appeared to affect working memory. Taken together, the results point to an involvement of hippocampal PKC in the acquisition of information destined for long-term storage.