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 th e nonselective CCK agonist BDNL were investigated in the elevated plus -maze in rats. BDNL and BC 197 induced anxiogeniclike effects, in cont rast to BC 264, which had no effect. The behavioral responses induced by BDNL were not significantly blocked by L-365,260, but were suppress ed 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]pB C 264 using brain membranes of guinea pig, mouse, and rat were signifi cantly better fitted when analyzed by a two site model than by a one s ite model with BC 197 but not with BC 264. Moreover, BC 264 produced a nxiogeniclike effects when administered with increasing doses of L-365 ,260 and opposing effects with increasing doses of CI-988. Together th ese results give pharmacological and behavioral evidence for the exist ence of CCK-B receptor subtypes.