Inhibitors of Cyclooxygenases produce Amnesia for a Passive Avoidance Task in the Chick

Abstract

Arachidonic acid is a putative messenger in synaptic transmission which presumably plays a role in learning and memory. Previous experiments showed that inhibitors of phospholipase A2-dependent release of arachidonic acid cause amnesia in a one-trial passive avoidance task in the chick. To test if arachidonic acid is metabolized to other messengers, the effects of inhibitors of enzymes which metabolize arachidonic acid were tested in the same task. The cyclooxygenase inhibitors indomethacin, naproxen and ibuprofen caused amnestic effects at all concentrations tested when injected intracerebrally before training. Injections were 5 microliters of 5-20 mmolar solutions per hemisphere. The onset of amnestic effects was always 2 h after training, independently of drug type, concentration, and injection time before training. The delay of 2 h after training suggests that the drugs prevent induction of cyclooxygenase synthesis. Post-training injections had no effect. Control tests showed little effect of the drugs on motor control and motivation. Caffeic acid and esculetin, inhibitors of lipoxygenases, and sodium furegrelate, a thromboxane synthase inhibitor, had no effect on performance of chicks in the task at all concentrations or time points tested. The results indicate that cyclooxygenase products, but not lipoxygenase or thromboxane synthase products, play a role in memory consolidation in the chick when learning this task.