Cholecystokinin-2 (CCK2) receptor-mediated anxiety-like behaviors in rats.

Abstract Cholecystokinin (CCK) is a neurotransmitter in the brain closely related to anxiety. Of the two CCK receptor subtypes, CCK 2 receptors are most implicated in the control of anxiety-related behavior. CCK 2 receptor activation causes anxiogenic effects while the blockade of this receptor has anxiolytic effects. This review focuses on the molecular mechanisms of CCK 2 receptors underlying anxiety-related behaviors of PVG hooded and Spraque–Dawley (SD) rats in two anxiety models (elevated plus-maze [EPM] and cat exposure test). PVG hooded rats showed prolonged freezing behavior in the cat exposure test while SD rats showed very low levels of freezing. A CCK 2 receptor antagonist (LY225910) attenuated freezing behavior in PVG hooded rats while a CCK 2 receptor agonist (CCK-4) increased freezing behavior in SD rats. In contrast, the two strains behaved similarly on the EPM. CCK-4 caused a pronounced anxiogenic effect in PVG hooded rats but only a slight effect in SD rats. CCK 2 antagonists also showed more pronounced anxiolytic effects in PVG hooded rats than in SD rats. CCK 2 receptor expression was greater in PVG hooded than in SD rats in the cortex and hippocampus. Genetic studies also demonstrated four differences in the DNA sequence of the CCK 2 receptor gene between the two rat strains.