Release of cholecystokinin in the central nervous system

The octapeptide cholecystokinin (CCK) is one of the most abundant neuropeptides of the central nervous system. A number of features (for instance heterogeneity of the regional distribution, subcellular localization at the nerve terminal level, calcium-dependent release upon nervous tissue depolarization) support the candidacy of CCK as a neurotransmitter. The reported co-existence of CCK and dopamine in some meso-limbic neurons has led to speculation that the neuropeptide may interact with the catecholamine in neuropsychopathologies linked to dopamine dysfunctions, like schizophrenia. Data from the experimental animals have so far generated conflicting results. It should be noted that the interactions between CCK and dopamine, and, in particular, the effects of CCK and dopamine on each other release, both in vitro and in vivo, have been poorly investigated and would require special attention. Evidence is accumulating that CCK may participate in the expression of anxiety. Indeed antagonists at the central CCK receptors exhibit anxiolytic activity in the laboratory animal. An interesting linkage appears to exist in the brain between 5-hydroxytryptamine (5-HT) and CCK. Activation of 5-HT3 receptors was found to increase CCK release from rat cortical or nucleus accumbens synaptosomes. Interestingly, antagonists at 5-HT3 receptors appear to possess anxiolytic activity. Recent studies carried out in conscious unrestrained rats show that the calcium-dependent, tetrodotoxin-sensitive release of CCK-like immunoreactivity evoked in the rat frontal cortex by veratrine infusion can be inhibited by submicromolar concentrations of 5-HT3 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)