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The Journal of Neuroscience, August 15, 1999, 19(16):7230-7237

Rat Hippocampal Neurons Are Critically Involved in Physiological Improvement of Memory Processes Induced by Cholecystokinin-B Receptor Stimulation

Angélique Sebret¹, Isabelle Léna¹, Dominique Crété¹, Toshimitsu Matsui², Bernard P. Roques¹, and Valérie Daugé¹

¹ Département de Pharmacochimie Moléculaire et Structurale, Institut National de la Santé et de la Recherche Médicale U266, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8600, Unité de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, 75270 Paris Cedex 06, France, and ² Third Division Department of Medicine, Kobe University School of Medicine, Kobe 650-0017 Japan

The involvement in memory processes of the neuropeptide cholecystokinin (CCK) through its interaction with the CCK-B receptors was studied. The two-trial recognition memory task was used. Control animals showed recognition memory 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 µg/kg) in the retrieval phase of the task (6 hr time interval), was also observed after its injection (1 pmol/0.5 µl) in the dorsal subiculum/CA1 of the hippocampus but not in the caudate/putamen nucleus or in the prefrontal cortex of rats. The CCK-B antagonist L-365,260 injected (10 ng/0.5 µl) into this region of the hippocampus abolished the improving effect of BC 264 injected intraperitoneally. Furthermore, L-365,260 injected in the hippocampus suppressed the recognition of the novel arm normally found in the controls (2 hr time interval) when it was injected before the acquisition or the retrieval phase of the task. In addition, an increase of the extracellular levels of CCK-like immunoreactivity in the hippocampus of rats during the acquisition and retention phase of the task was observed. Finally, CCK-B receptor-deficient mice have an impairment of performance in the memory task (2 hr time interval).

Together, these results support the physiological involvement of the CCKergic system through its interaction with CCK-B receptors in the hippocampus to improve performance of rodents in the spatial recognition memory test.

Key words: cholecystokinin-B receptors; spatial memory; CA1; prelimbic-infralimbic cortex; CCK release; CCK-B receptor-deficient mice

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19167230-08$05.00/0

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