Cholecystokinin (CCK) as an important neuropeptide in the brain has been implicated in the modulation of anxiety. The effects of this neurotransmitter on anxiety-like behavior in the ventral hippocampus have not been evaluated yet. Moreover, some evidences show a functional interaction between GABA and CCK in the nervous system. Bilateral injections of three doses of CCK8s (0.01, 0.05 and 0.1 μg/rat) into the ventral hippocampus decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior in the elevated plus-maze test of anxiety. Bilateral injections of LY225910, a selective CCK2 receptor antagonist, at the doses of 0.01, 0.1 and 0.5 μg/rat did not change anxiety-related parameters. Administration of muscimol, a selective GABAA receptor agonist, at the doses of 0.001, 0.005 and 0.01 μg/rat produced dose dependent increase in %OAT and %OAE indicating an anxiolytic-like effect, while administration of bicuculline, a selective GABAA receptor antagonist, at the doses of 0.1, 0.2 and 0.5 μg/rat decreased %OAT and%OAE showing that this drug promoted anxious behavior of the rats. Co-administration of bicuculline (0.2 μg/rat) with CCK8s decreased the anxiogenic effects of CCK8s. Furthermore, coadministration of LY225910 (0.5 μg/rat) with muscimol increased the anxiolytic effect of muscimol at the dose of 0.001 μg/rat. The results of this study suggest that both CCK and GABAergic system have important and opposite roles in the modulation of anxietylike behavior in the ventral hippocampus of rats and they may have a complex interaction in the ventral hippocampus to modulate anxiety-related behavior.
