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, 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.