Daugé V, Derrien M, Blanchard J C, Roques B P
Laboratoire de Pharmacochimie Moléculaire, U266 INSERM, CNRS, Université René Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Neuropharmacology. 1992 Jan;31(1):67-75. doi: 10.1016/0028-3908(92)90163-j.
The aim of this study was to examine the behavioural effects induced by stimulation of CCK receptors in the nucleus accumbens of the rat, which contains a high density of heterogenously distributed CCK-B receptors. The drug BC264 (Boc-Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2), a highly potent and selective CCK-B agonist, injected into the postero-median or antero-median n. accumbens did not modify the spontaneous alternation and exploratory behaviour observed in a Y-maze. In contrast, when administered into the antero-lateral part of the n. accumbens, BC264 (0.3-1.0 nmol) reduced alternation to chance level, without changing the number of arm visits. This effect was suppressed by the selective CCK-B antagonist: L365,260, but not by the selective CCK-A antagonist: MK329. The physiological relevance of this effect was supported by the similar responses induced, in the same concentration range, by the CCK8-like agonist, BDNL (Boc diNle28,31CCK7). These results emphasize the functional heterogeneity of the CCK network in the n. accumbens of the rat and the participation of the peptide in the expression of alternation behaviour, through stimulation of CCK-B receptors. They also show that the recently described anxiolytic effects, induced by CCK-B antagonists, do not seem to occur at this level.
本研究的目的是检测刺激大鼠伏隔核中的胆囊收缩素（CCK）受体所诱导的行为效应，该伏隔核含有高密度的异质性分布的CCK-B受体。将药物BC264（Boc-Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2），一种高效且选择性的CCK-B激动剂，注射到伏隔核后内侧或前内侧，并不会改变在Y迷宫中观察到的自发交替和探索行为。相反，当将BC264（0.3 - 1.0 nmol）注射到伏隔核的前外侧部分时，会将交替行为降低到随机水平，而不改变进入臂的次数。这种效应被选择性CCK-B拮抗剂L365,260所抑制，但不被选择性CCK-A拮抗剂MK329所抑制。在相同浓度范围内，CCK8样激动剂BDNL（Boc diNle28,31CCK7）诱导出的类似反应支持了这种效应的生理相关性。这些结果强调了大鼠伏隔核中CCK网络的功能异质性，以及该肽通过刺激CCK-B受体参与交替行为的表达。它们还表明，最近所描述的由CCK-B拮抗剂诱导的抗焦虑作用似乎并未在此水平发生。
