BRAIN CHOLECYSTOKININ SYSTEM IN NEUROTIC PATHOLOGY

Abstract

Violation and discoordination of mental processes leads to changes in the ratio of the main neurotransmitters content and further to mental disorders. A significant role in such processes is played by neuropeptides, in particular anti-anxiety ones, which include cholecystokinin (CCK) and its receptors. It has been established that stimulation of CCK receptors modulates the mesolimbic system of reward, anxiety and satiety. CCK-1 (the intestine) and CCK-2 type receptors (the CNS and stomach) are isolated. In the central nervous system, the short O-sulfated form of CCK-8 and the non-sulfated form of CCK-5 predominate. It was shown that the effect of CCK on the corresponding receptors inhibits GABA-ergic receptors in the subcortical nuclei, which mediates the transmission of nerve signals from the endocannabinoid system. A significant number of CCK receptors, their agonists and antagonists were found in the body. Potentially, blockers of these receptors can be combined with other agents for the treatment of CNS diseases. In CCK, it was shown an anxiogenic effect, which was realized through the influence of a selective CCK-2 receptors agonist. There is information that CCK-4 causes anxiogenic effects due to its influence on other neurotransmitters, in particular, due to neuromodulation of the dopaminergic system, and can interact with other neurotransmission systems. In behavioral tests, the anxiolytic effect of CCK-2 receptor blockers is shown. The participation of this system in the pathogenesis of anxiety is confirmed by the influence of non-selective agonists of CCK receptors and agonists of CCK-2 receptors in the "elevated cross-shaped maze" test. At the same time, CCK-2 receptor blockers reduced anxiety in this test. In clinical studies, they suppressed panic when administered as a bolus. However, the problem of bioavailability of compounds remains unsolved. The significant diversity of CCK receptors and their expression in all parts of the brain also complicates their application greatly. So, the CCK system of the brain is involved in the development of the main manifestations of anxiety pathology, but there are prospects for the medical use of substances that regulate the functional activity of CCK receptors.