Anxiogenic effect of CCK8s in the ventral hippocampus of rats: possible involvement of GABA(A) receptors.

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 CCK(2) 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 GABA(A) 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 GABA(A) 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, co-administration 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 anxiety-like behavior in the ventral hippocampus of rats and they may have a complex interaction in the ventral hippocampus to modulate anxiety-related behavior.