Privette T H, Terrian D M
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
Psychopharmacology (Berl). 1995 Apr;118(4):444-50. doi: 10.1007/BF02245945.
The selective kappa agonist U-50,488H was evaluated on the elevated plus-maze test of anxiety. U-50,488H was administered intraperitoneally to male Sprague-Dawley rats 20 min before testing, first in an open field apparatus, then followed immediately on the elevated plus-maze. No significant change in spontaneous locomotor activity was measured in the open field apparatus, suggesting that U-50,488H was devoid of sedative effects in the dose range tested (0.1-1000 micrograms/kg, IP). Doses between 10 and 1000 micrograms/kg produced significant increases in elevated plus-maze behavior that were consistent with anxiolytic actions for U-50,488H. These anxiolytic-like effects were antagonized by naloxone (2.0 mg/kg, IP), suggesting an opioid receptor site of action. In addition, we tested the kappa 1-selective U-50,488H-derivative, U-69,593 (100 micrograms/kg, IP), which was also shown to mimic the anxiolytic-like effects produced by U-50,488H. These results suggest that low doses of the selective kappa 1 agonists U-50,488H and U-69,593 are endowed with anxiolytic properties in rodents and that the kappa opioid system may be involved in the behavioral response to anxiety.
在高架十字迷宫焦虑测试中对选择性κ激动剂U - 50,488H进行了评估。在测试前20分钟，对雄性斯普拉格 - 道利大鼠腹腔注射U - 50,488H，首先在旷场装置中进行，然后立即进行高架十字迷宫实验。在旷场装置中未检测到自发运动活动有显著变化，这表明在所测试的剂量范围（0.1 - 1000微克/千克，腹腔注射）内，U - 50,488H没有镇静作用。10至1000微克/千克的剂量使高架十字迷宫行为显著增加，这与U - 50,488H的抗焦虑作用一致。这些抗焦虑样作用被纳洛酮（2.0毫克/千克，腹腔注射）拮抗，表明其作用位点为阿片受体。此外，我们测试了κ1选择性U - 50,488H衍生物U - 69,593（100微克/千克，腹腔注射），它也表现出模拟U - 50,488H产生的抗焦虑样作用。这些结果表明，低剂量的选择性κ1激动剂U - 50,488H和U - 69,593在啮齿动物中具有抗焦虑特性，并且κ阿片系统可能参与对焦虑的行为反应。
