L364,718 antagonizes the cholecystokinin-induced suppression of locomotor activity

To determine the role of CCK-A receptors in the cholecystokinin (CCK)-induced suppression of locomotor activity in the rat, the ability of the selective CCK-A receptor antagonist L364,718 to block these responses was investigated. Cholecystokinin octapeptide (CCK8) (10,100 μg/kg IP) and caerulein (1, 5, 10 μg/kg IP) produced marked reductions in locomotor activity whereas cholecystokinin tetrapeptide (CCK4) (100 μg/kg IP) was without effect. The reductions in activity produced by CCK8 (10 μg/kg) and caerulein (10 μg/kg) were antagonized by L364,718 (100 μg/kg IP). In an open field test CCK8 (10 μg/kg IP) reduced locomotor activity and total number of rears and increased pause duration. These effects of CCK8 on open-field behaviour were also antagonized by L364,718 (100 μg/kg IP). It is concluded that L364,718 is a potent antagonist of the actions of CCK8 and caerulein on locomotor activity, suggesting that the effects of these peptides are mediated by a CCK-A receptor.