Opposite effects of CCK B agonists in grooming behaviour in rats: further evidence for two CCK B subsites

1 The hypothesis of the existence of two CCK B receptor subsites, CCK B1 and CCK B2 corresponding probably to different coupling states of CCK B receptors, was studied by measuring grooming behaviour in rats. 2 The B1 receptor agonist, BC197 (300 μg kg −1 , i.p.) produced a 45–50% decrease in grooming activity, which was prevented by both the CCK B receptor antagonists CI‐988 (20 μg kg −1 i.p.) and L‐365,260 (200 μg kg −1 , i.p.). 3 In contrast, 3, 10 and 30 μg kg −1 , i.p., of the potent B2 receptor agonist, BC264, enhanced grooming (150–190%). This effect was prevented by previous injection of 75 μg kg −1 of L‐365,260 while higher doses (200 μg kg −1 , i.p.) produced only a partial antagonism. Moreover, CI‐988 (20 μg kg −1 , i.p.), showed an opposite effect in potentiating the responses induced by BC264. However, 200 μg kg −1 of CI‐988 tended to suppress the increase of grooming induced by BC264. 4 The effects of BC264 were prevented by the D 1 receptor (SCH 23390) and D 2 receptor (sulpiride) antagonists, while those of BC197 were only antagonized by sulpiride, emphasizing the existence of a link between peptidergic (CCK) and dopaminergic systems. 5 This study brings additional evidence for the existence of the two CCK B receptor subsites and suggests that particular attention should be focused on the selectivity of CCK B receptor agonists, notably to explain the fact that some compounds such as Boc‐CCK4 induce anxiogenic‐like effects while others, including BC264, are devoid of these effects.British Journal of Pharmacology (1998) 124 , 1091–1098; doi: 10.1038/sj.bjp.0701933