The peptide cholecystokinin (CCK)2was originally discovered in the gastrointestinal tract ([Ivy and Oldberg, 1928][1]) and has been shown to mediate pancreatic secretion and contraction of gallbladder. Then, CCK was described in the mammalian central nervous system (CNS) as a gastrin-like

https://pharmrev.aspetjournals.org/content/pharmrev/51/4/745.full.pdf

International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors.

CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology

It is well documented that stressful life experiences contribute to the etiology of human mood disorders. Cholecystokinin (CCK) is a neuropeptide found in high concentrations throughout the central nervous system, where it is involved in numerous physiological functions. A role for CCK in the induction and persistence of anxiety and major depression appears to be conspicuous. While increased CCK has been associated with motivational loss, anxiety and panic attacks, an increase in mesocorticolimbic opioid availability has been associated with coping and mood elevation. The close neuroanatomical distribution of CCK with opioid peptides in the limbic system suggests that there may be an opioid-CCK link in the modulation and expression of anxiety or stressor-related behaviors. In effect, while CCK induces relatively protracted behavioral disturbances in both animal and human subjects following stressor applications, opioid receptor activation may change the course of psychopathology. The antagonistic interaction of CCK and opioid peptides is evident in psychological disturbances as well as stress-induced analgesia. There appears to be an intricate balance between the memory-enhancing and anxiety-provoking effects of CCK on one hand, and the amnesic and anxiolytic effects of opioid peptides on the other hand. Potential anxiogenic and mnemonic influences of site-specific mesocorticolimbic CCK and opioid peptide availability, the relative contributions of specific CCK and opioid receptors, as well as the time course underlying neuronal substrates of long-term behavioral disturbances as a result of stressor manipulations, are discussed.

Cholecystokinin and endogenous opioid peptides: interactive influence on pain, cognition, and emotion.

CCK in anxiety and cognitive processes.

List of questions G-protein-coupled receptors (GPCRs) comprise the largest single class of cell-surface receptors, and have a history of being excellent therapeutic targets for a number of diseases. Yet several fundamental questions remain regarding their underlying biology, and many GPCRs that could be promising targets for drug discovery are still uncharacterized at the level of identified ligand or biological function. In an attempt to find some answers, we posed 20 questions of fundamental importance to the future development of the field to 20 of the world's leading experts on GPCR research, and here we present their replies.

The state of GPCR research in 2004

Rationale: The implication of CCKB receptors in cognitive processes is far from fully understood. Objective: The present study investigated the effect of propionyl-BC264, a selective agonist of CCKB receptors, in young and old rats. Methods: Cognitive functions were studied in a two-trial recognition memory task developed in our laboratory. Results: It was shown that propionyl-BC264 enhanced information processing in young as well as in old rats when injected (10 μg/kg; IP) immediately after the acquisition phase and before the retrieval trial but not before the acquisition trial. This cognitive enhancing effect was blocked by prior administration of L 365,260, a selective CCKB receptor antagonist. Conclusions: In view of the fact that BC264 is devoid of anxiogenic effects, it could be of value in the treatment of cognitive impairments associated with both normal and pathological ageing.

K. Taghzouti

Papers

Cognitive enhancing effects in young and old rats of pBC264, a selective CCKB receptor agonist