Rat hippocampal neurons are critically involved in physiological improvement of memory processes induced by cholecystokinin-B receptor stimulation

The involvement in memory processes of the neuropeptide cholecystokinin (CC K) through its interaction with the CCK-B receptors was studied. The two-tr ial recognition memory task was used. Control animals showed recognition me mory after a 2 hr time interval but not after a 6 hr time interval between the two trials. The improving effect of a selective CCK-B agonist, BC 264, intraperitoneally administered (0.3 mu g/kg) in the retrieval phase of the task (6 hr time interval), was also observed after its injection (1 pmol/0. 5 mu l) in the dorsal subiculum/CA1 of the hippocampus but not in the cauda te/putamen nucleus or in the prefrontal cortex of rats. The CCK-B antagonis t L-365,260 injected (10 ng/0.5 mu l) into this region of the hippocampus a bolished the improving effect of BC 264 injected intraperitoneally. Further more, L-365,260 injected in the hippocampus suppressed the recognition of t he novel arm normally found in the controls (2 hr time interval) when it wa s injected before the acquisition or the retrieval phase of the task. In ad dition, an increase of the extracellular levels of CCK-like immunoreactivit y in the hippocampus of rats during the acquisition and retention phase of the task was observed. Finally, CCK-B receptor-deficient mice have an impai rment of performance in the memory task (2 hr time interval). Together, these results support the physiological involvement of the CCKerg ic system through its interaction with CCK-B receptors in the hippocampus t o improve performance of rodents in the spatial recognition memory test.