HETEROGENEITY OF CCK-B RECEPTORS INVOLVED IN ANIMAL-MODELS OF ANXIETY

The effects of the selective CCK-B agonists, BC 264 and BC 197, and the nonselective CCK agonist BDNL were investigated in the elevated plus-maze in rats. BDNL and BC 197 induced anxiogeniclike effects, in contrast to BC 264, which had no effect. The behavioral responses induced by BDNL were not significantly blocked by L-365,260, but were suppressed by CI-988, another selective CCK-B antagonist, and by high doses of L-364,718, a selective CCK-A antagonist. BC 197-induced effects were also blocked by CI-988. Competition experiments performed with [H-3]pBC 264 using brain membranes of guinea pig, mouse, and rat were significantly better fitted when analyzed by a two site model than by a one site model with BC 197 but not with BC 264. Moreover, BC 264 produced anxiogeniclike effects when administered with increasing doses of L-365,260 and opposing effects with increasing doses of CI-988. Together these results give pharmacological and behavioral evidence for the existence of CCK-B receptor subtypes.