CCK-A and CCK-B receptors enhance olfactory recognition via distinct neuronal pathways

We have previously reported that CCK-A receptor agonists and CCK-B receptor antagonists both enhance memory in an olfactory recognition test. Here, we report that the memory-enhancing effect of the CCK-B receptor antagonist L-365,260 (1 mg/kg i.p.), but not that of the CCK-A receptor agonist caerulein (0.03 mg/kg i.p.), was dramatically decreased following a bilateral transection of the perforant path, a principal source of input to the hippocampal formation. We further confirmed that a significant memory deficit occurred subsequent to this deafferentation of the hippocampus in untreated animals. In contrast, the effect of caerulein, but not that of L-365,260, was abolished following a bilateral subdiaphragmatic vagotomy. These results demonstrate that the hippocampal system plays a role in olfactory recognition and indicate that distinct neuronal pathways underlie the memory-enhancing effects of CCK-A and CCK-B drugs observed in the olfactory recognition test. The former effects (CCK-A) appear to involve a peripheral relay to the brain via the vagus nerve, whereas the latter (CCK-B) are directly central and involve, at least in part, the hippocampal system.