INHIBITORS OF PHOSPHOLIPASE A(2) PRODUCE AMNESIA FOR A PASSIVE-AVOIDANCE TASK IN THE CHICK

The effects of blocking phospholipase A(2) (PLA(2)), a key enzyme in arachidonic acid (ArA) release, on memory retention have been studied in a one-trial passive avoidance task in the day-old chick. Bilateral intracerebral injections of the PLA(2) and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) (15 mu l of 4 mM NDGA/hemisphere, calculated to give an equivalent intracerebral concentration of 120 mu M) or the PLA(2) inhibitor aristolochic acid (AST) (5 mu l of a 4 mM AST/hemisphere, calculated to give an equivalent intracerebral concentration of similar to 40 mu M) were made into the intermediate medial hyperstriatum ventrale (IMHV), an area that is of crucial importance for memory formation in the chick in this task. Pretraining injections of either inhibitor resulted in the chicks showing lasting amnesia for the avoidance response. The onset of amnesia with both inhibitors NDGA and AST was at 1.25 h post-training. Injection of drugs post-training had no effect on retention. Time and dose dependencies of both drugs were evaluated. Additional tests showed that the amnestic effect is not due to state-dependent learning nor to interference of the drugs with general motor ability or motivation. The results support the theory that arachidonic acid release is a necessary step in the early, although not immediate, events mediating the synaptic plasticity associated with memory formation. This is compatible with the hypothesis that ArA may serve as a late retrograde messenger between post- and presynaptic sites of plasticity, although it is not proof of such a role. (C) 1994 Academic Press, Inc.