The ACTH 4–9 analog ORG 2766 ‘normalizes’ the changes in motor activities of rats elicited by housing and test conditions

Abstract

Motor activities of rats were decreased by short-term (7 days) social isolation as well as by intense light test conditions. The ACTH 4-9 analog ORG 2766, s.c. administered 50 min before testing, dose-dependently decreased the high motor activities of group-housed housed rats tested under low light conditions and increase the low motor activities of short-term isolated rats tested under intense light conditions (ED 50: 0.01–0.03 μg/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 ACTH 4–10 (100 μg/kg) tended to enhance some of the effects of the environmental conditions. Pretreatment of rats with the opioid antagonist naltrexone (450μg/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.