Effects of Posttraining Intrahippocampal Injections of Platelet-Activating Factor and PAF Antagonists on Memory

The present experiments examined the effects of posttraining intrahippocampal injections of the degradative enzyme-resistant methylcarbamyl analog of the bioactive phospholipid platelet-activating factor (mc-PAF) and the platelet-activating factor (PAF) receptor antagonists BN52021 and BN 50730 on memory in male Long-Evans rats trained in a hidden platform version of the Morris water maze. Following an eight-trial training session, rats received a unilateral intrahippocampal injection of mc-PAF (0.5, 1.0, or 2.0 μg/0.5 μl), lyso-PAF (1.0 μg/0.5 μl), the cell surface PAF receptor antagonist BN 52021 (0.25, 0.5, or 1.0 μg/0.5 μl), the intracellular PAF receptor antagonist BN 50730 (2.0, 5.0, or 10.0 μg/0.5 μl), or vehicle (50% DMSO in 0.9% saline; 0.5 μl). On a retention test conducted 24 h after training, the escape latencies of rats administered mc-PAF (1.0 or 2.0 μg) were significantly lower than those of the vehicle-injected controls, demonstrating a memory-enhancing effect of mc-PAF. Injections of lyso-PAF, a structurally similar metabolite of PAF, had no influence on memory, indicating that the memory-enhancing effect of mc-PAF is not caused by membrane perturbation by the phospholipid. The retention test escape latencies of rats administered BN 52021 (0.5 μg) and BN 50730 (5.0 or 10 μg) were significantly higher than those of the controls, indicating a memory impairing effect of both PAF antagonists. When mc-PAF, BN 52021, or BN 50730 was administered 2 h posttraining, no effect on retention was observed, indicating a time-dependent effect of the neuroactive substances on memory storage. The findings suggest a role for endogenous PAF in hippocampal-dependent memory processes.