cholecystokinin and Memory-Disorders

The neuropeptide Cholecystokinin (CCK) is involved in the modulation of memory processes. In this study, we examined for the first time the effect of intranasally administered CCK on controlled recollection and automatic familiarity in humans. To separate controlled from automatic memory processes, we used a modified version of Jacoby's process dissociation procedure (1991). Immediately after two successive learning phases, which are necessary for the implementation of the procedure, half of the participants received CCK, the other half a placebo solution. Recognition was tested 30 min after the learning phases. CCK decreased controlled recollection but not automatic familiarity when compared to placebo. Behavioral, physiological, and subjective control variables were not affected by the peptide. The results indicate a differential effect of CCK on controlled memory processes. Either consolidation and/or retrieval of verbal material are impaired.

Topics: Administration, Intranasal; Adolescent; Adult; Blood Pressure; Cholecystokinin; Double-Blind Method; Female; Gastrointestinal Agents; Heart Rate; Humans; Hydrocortisone; Male; Memory Disorders; Recognition, Psychology; Saliva; Severity of Illness Index

Acute and chronic exposure to opiate drugs impaired various types of memory processes. To date, there is no preventive treatment for opiate-induced memory impairment and the related mechanism is still unclear. CCK-8 is the most potent endogenous anti-opioid peptide and has been shown to exert memory-enhancing effect, but the effect of CCK-8 on morphine-induced memory impairment has not been reported. By using Morris water maze, we found that escape latency to the hidden platform in navigation test was not influenced, but performance in the probe test was seriously poor in morphine dependency mice. Amnesia induced by chronic morphine treatment was significantly alleviated by pre-treatment with CCK-8 (0.01, 0.1 and 1 μg, i.c.v.), and CCK-8 (0.1 and 1 μg, i.c.v.) treatment alone could improve performance in either navigation or probe test. Furthermore, Golgi-Cox staining analysis revealed that pre-treatment with CCK-8 (1 μg, i.c.v.) reversed spine density decreased in CA1 region of hippocampus in morphine dependency mice, and CCK-8 (1 μg, i.c.v.) alone obviously increased spine density in CA1. Our findings conclude spine density change in CA1 region of hippocampus may be the structural plasticity mechanism which is responsible for enhancing effect of CCK-8 on spatial reference memory. Therefore, CCK-8 could effectively improve memory impairment in morphine dependency mice.

Topics: Animals; Behavior, Animal; CA1 Region, Hippocampal; Cholecystokinin; Dendritic Spines; Male; Maze Learning; Memory; Memory Disorders; Mice; Morphine; Peptide Fragments; Spatial Behavior

The central fragment of cholecystokinin, CCK8, plays a critical role in stress-related changes in behavior and memory. Therefore, we investigated whether the endogenous cholecystokininergic system is involved in the impairment of attention and/or memory induced by stressful conditions. Plasma corticosterone concentrations increased three-fold and plasma adrenocorticotropin (ACTH); concentrations increased five-fold when rats were maintained in the open arm of an elevated plus maze for 5 min. The same stress conditions impaired spatial recognition in the two-trial memory task. In addition, this stress led to a significant decrease in the extracellular levels of cholecystokinin-like immunoreactivity in the dorsal subiculum/CA1 of the hippocampus and partially suppressed the increase obtained during the acquisition phase of memory. This suggests that the cholecystokininergic system in the hippocampus is involved in stress-induced impairment of spatial recognition memory.

Topics: Adrenocorticotropic Hormone; Animals; Brain; Cholecystokinin; Corticosterone; Down-Regulation; Hippocampus; Male; Maze Learning; Memory Disorders; Neural Pathways; Rats; Rats, Wistar; Stress, Physiological