2 FACES OF CHOLECYSTOKININ - ANXIETY AND SCHIZOPHRENIA

It has been suggested that cholecystokinin (CCK), a gut-brain peptide found in high concentrations in the mammalian brain, might be implicat ed in the neurobiology of anxiety and panic disorder. The administrati on of CCK tetrapeptide induced panic attacks analogous to spontaneous ones in patients suffering from panic disorder and to a lesser degree in healthy volunteers. In animal models of anxiety, the pretreatment w ith CCK agonists and antagonists produced, respectively, anxiogenic- a nd anxiolytic-like action on the exploratory paradigms. On the other h and, CCK could also play a role in the pathophysiology of schizophreni a. The administration of CCK agonists (caerulein, CCK-8s) to rodents r esults in behavioural effects analogous to those of antipsychotic drug s. However, CCK agonists lack any activity in rodent behavioural model s to reveal antipsychotic drugs. A significant reduction of CCK concen tration and CCK receptors has been shown in cortical and limbic struct ures of patients suffering from schizophrenia. Nevertheless, administr ation of CCK agonists to these patients does not effect their symptoms . Two major conclusions should be drawn: first, CCK is involved in the neurobiology of anxiety; second, changes in the CCK system in schizop hrenia could be linked to a cortical neurodegeneration related to this disease.