Singh L, Lewis A S, Field M J, Hughes J, Woodruff G N
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1130-3. doi: 10.1073/pnas.88.4.1130.
The effect of neuropeptide cholecystokinin (CCK) receptor agonists and antagonists was examined in the rat elevated X-maze model of anxiety. The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200. The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to pentagastrin but not that induced by pentylenetetrazol. These results strongly suggest that activation of the brain CCK-B receptor induces anxiety and that selective antagonists of this receptor represent a separate class of anxiolytic agents.
在大鼠高架十字迷宫焦虑模型中研究了神经肽胆囊收缩素(CCK)受体激动剂和拮抗剂的作用。选择性CCK - B受体拮抗剂CI - 988(PD 134308)和L - 365,260产生抗焦虑样作用,而CCK - A受体拮抗剂MK - 329的效力分别低313倍和200倍。脑室内注射非选择性CCK受体激动剂蛙皮素或选择性CCK - B受体激动剂五肽胃泌素可使焦虑水平剂量依赖性增加。CI - 988剂量依赖性地拮抗五肽胃泌素引起的致焦虑反应,但不拮抗戊四氮诱导的反应。这些结果强烈表明,脑CCK - B受体的激活诱导焦虑,并且该受体的选择性拮抗剂代表一类单独的抗焦虑药物。