Investigation of behavioral and electrophysiological responses induced by selective stimulation of CCKB receptors by using a new highly potent CCK analog, BC 264.

The new CCKB analog, Boc-Tyr (SO3H)-gNle-mGly-Trp-(NMe)-Nle-Asp-PheNH2 (BC 264) exhibited a high affinity (KI = 0.39 +/- 0.15 nM) and selectivity for central (B) versus peripheral (A) receptors (KI CCKA/KI CCKB = 910) in the rat. In agreement with these binding studies, BC 264 was at least 50 times more potent than CCK8 in stimulating the firing of rat CA hippocampal neurones. Furthermore stereotaxic injection of BC 264 or CCK8 in the VTA of rats resulted in potentiation of the dopamine-induced hypolocomotion. These two types of CCK8 responses have been previously shown in involve CCKB receptors. In contrast, after administration into the postero-median nucleus accumbens, the hypoexploration, the increase of emotionality of rats, or the potentiation of dopamine-induced hyperlocomotion were obtained after injection of CCK8 but not of BC 264, supporting the involvement of peripheral CCKA receptors in these CCK8 responses. Owing to its resistance to peptidases, BC 264 appears to be of great interest in the investigation of the still uncertain functional roles of CCK in the central nervous system.