INFLUENCES OF CHOLECYSTOKININ AND ANALOGS ON MEMORY PROCESSES

Evidence is reviewed to assign the role of cholecystokinins in the cognitive and memory processes. Rat brain contains about 550 ng of CCK-8. When injected, icv or sc, in doses of less than 100 ng of CCK or caerulein, these peptides prevent experimental amnesia and prolong extinction of the already-learned tasks. Caerulein is nearly 10 times as potent as CCK-8, and the effects of both peptides are long-lasting. Pretreatment with these peptides also prevents scopolamine-induced amnesia, and reverses the ACh depletion in the frontal and temporal cortices as well as in the hippocampus. CCK-8 antagonists in small doses produce complete amnesia, further supporting the hypothesis that endogenous CCK-8 modulates the memory processes in the brain. Neurochemical data suggest participation of the NMDA receptors, protein kinase C, and protein synthesis in the action of CCK-8 and caerulein. Sub-diaphragmatical vagotomy abolishes the memory-enhancing effects of these peptides when administered peripherally. Thus, CCK-8 and caerulein are likely to affect not only the receptors localized in the CNs, but also to stimulate peripheral receptors associated with the vagus. Alternatively, the vagus may be the major pathway for CCK transport form the visceral organs to the brain.