Intrahippocampal, but not intra-amygdala, infusion of an inhibitor of heme oxygenase causes retrograde amnesia in the rat.

Zinc protoporhyrin-9 (ZnPP) is an inhibitor of heme oxygenase, the enzyme involved in the biosynthesis of carbon monoxide (CO). CO regulates the activity of glutamatergic synapses and has been proposed to play a role in the early phases of long-term potentiation. The present paper reports on the effect of ZnPP on memory of inhibitory avoidance and of habituation to a novel environment. The bilateral infusion of ZnPP (2 micrograms/side) into the dorsal hippocampus caused amnesia for the inhibitory avoidance task when given before training or 0 or 30 min, but not 60 or 100 min, after training. The immediate post-training intrahippocampal infusion of ZnPP also caused amnesia for the habituation task. The immediate post-training intra-amygdala infusion of ZnPP had no effect on retention of the avoidance task. The data are consistent with the hypotheses that memory involves long-term potentiation initiated at the time of training in the hippocampus, and that hippocampal but not amygdala long-term potentiation may be regulated by CO.