Opposite effects of CCKB agonists in grooming behaviour in rats: further evidence for two CCKB subsites |
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Authors: | Nathalie Ladurelle Angélique Sebret Christiane Garbay Bernard P Roques Valérie Daugé |
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Institution: | 1.Département de Pharmacochimie Moléculaire et Structurale, U 266 INSERM, URA D 1500 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4, avenue de l''Observatoire–75270 Paris Cedex 06, France |
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Abstract: | - The hypothesis of the existence of two CCKB receptor subsites, CCKB1 and CCKB2 corresponding probably to different coupling states of CCKB receptors, was studied by measuring grooming behaviour in rats.
- 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 CCKB receptor antagonists CI-988 (20 μg kg−1 i.p.) and L-365,260 (200 μg kg−1, i.p.).
- 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.
- The effects of BC264 were prevented by the D1 receptor (SCH 23390) and D2 receptor (sulpiride) antagonists, while those of BC197 were only antagonized by sulpiride, emphasizing the existence of a link between peptidergic (CCK) and dopaminergic systems.
- This study brings additional evidence for the existence of the two CCKB receptor subsites and suggests that particular attention should be focused on the selectivity of CCKB 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.
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Keywords: | CCKB receptor subsites BC197 BC264 grooming activity dopamine |
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