Wolterink G, Van Ree J M
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Brain Res. 1987 Sep 22;421(1-2):41-7. doi: 10.1016/0006-8993(87)91272-8.
Motor activities of rats were decreased by short-term (7 days) social isolation as well as by intense light test conditions. The ACTH4-9 analog ORG 2766, s.c. administered 50 min before testing, dose-dependently decreased the high motor activities of group-housed rats tested under low light conditions and increased the low motor activities of short-term isolated rats tested under intense light conditions (ED50: 0.01-0.03 microgram/kg). Structure-activity studies suggest that the essential structure for these effects may be located in the C-terminal tripeptide Phe-D-Lys-Phe. Treatment with ACTH4-10 (100 micrograms/kg) tended to enhance some of the effects of the environmental conditions. Pretreatment of rats with the opioid antagonist naltrexone (450 micrograms/kg, s.c.) completely blocked the 'normalizing' effects of ORG 2766, implicating endogenous opioids in this action of ORG 2766. Since social behaviors of rats are similarly affected by ORG 2766 as motor activities, it is suggested that this peptide affects the integration of sensoric stimuli rather than the specific motor output systems of these behaviors.
短期（7天）的社会隔离以及强光测试条件会降低大鼠的运动活动。促肾上腺皮质激素4-9类似物ORG 2766，在测试前50分钟皮下注射，剂量依赖性地降低了在弱光条件下测试的群居大鼠的高运动活动，并增加了在强光条件下测试的短期隔离大鼠的低运动活动（半数有效剂量：0.01 - 0.03微克/千克）。构效关系研究表明，这些效应的基本结构可能位于C末端三肽苯丙氨酸-D-赖氨酸-苯丙氨酸。用促肾上腺皮质激素4-10（100微克/千克）处理倾向于增强环境条件的一些效应。用阿片类拮抗剂纳曲酮（450微克/千克，皮下注射）对大鼠进行预处理完全阻断了ORG 2766的“正常化”效应，表明内源性阿片类物质参与了ORG 2766的这一作用。由于大鼠的社会行为与运动活动同样受到ORG 2766的影响，因此提示该肽影响感觉刺激的整合，而非这些行为的特定运动输出系统。
