Docosahexaenoic acid improves long‐term potentiation attenuated by phospholipase A2 inhibitor in rat hippocampal slices

We investigated the possible involvement of phospholipase A2 (PLA2) and its products in long‐term potentiation (LTP) in the CA1 neurotransmission of rat hippocampal slices. Inhibitors of Ca2+‐independent PLA2 (iPLA2) prevented the induction of LTP without affecting the maintenance phase of LTP whereas Ca2+‐dependent PLA2 inhibitors were virtually ineffective, which suggests a pivotal role of iPLA2 in the initiation of LTP. We then investigated the effect of docosahexaenoic acid (DHA) and arachidonic acid (AA) on BEL (bromoenol lactone, an iPLA2‐inhibitor) ‐impaired LTP, and found that either DHA or AA abolished the effect of BEL. However, DHA did not restore BEL‐attenuated LTP when applied after the tetanus. DHA per se affected neither the induction nor maintenance of LTP. Linoleic acid had no effects, either. These results suggest that DHA is crucial for the induction of LTP and that endogenously released DHA during tetanus is sufficient to trigger the formation of LTP. British Journal of Pharmacology (2001) 132, 1417–1422; doi:10.1038/sj.bjp.0703970