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

Cholecystokinin (CCK) is a neurotransmitter in the brain closely related to anxiety. Of the two CCK receptor subtypes, CCK2 receptors are most implicated in the control of anxiety-related behavior. CCK2 receptor activation causes anxiogenic effects while the blockade of this receptor has anxiolytic effects. This review focuses on the molecular mechanisms of CCK2 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 CCK2 receptor antagonist (LY225910) attenuated freezing behavior in PVG hooded rats while a CCK2 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. CCK2 antagonists also showed more pronounced anxiolytic effects in PVG hooded rats than in SD rats. CCK2 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 CCK2 receptor gene between the two rat strains.