Analysis of the facilitatory effect of the ACTH-(4–9) analog ORG 2766 on active social contact in rats

Abstract

Pairs of male rats were tested for active social interaction, either in a familiar test arena under low illumination or in an unfamiliar test arena under high illumination conditions. Rats tested in an unfamiliar environment and under high light, spent less time in active social contact than rats tested under familiar, low light conditions. This effect was not pronounced during the first half of the 10 minute test period. Intraperitoneal injections of ACTH-(1–24) and ACTH-(4–10) (50 μg/kg) administered 5 minutes before the test decreased, whereas the same dose of the synthetic ACTH-(4–9) analog ORG 2766 increased the time spent in active social contact, when rats were tested under unfamiliar, high light conditions. The effects of ACTH-(4–10) and ORG 2766 were present in the second and first half of the test period respectively. Dose response relationship studies with ORG 2766 showed that 0.5 μg/kg of this peptide facilitated social contact under both test conditions and the dose response relation followed an inverted U-shaped curve under the familiar low light condition, but not under the unfamiliar, high light condition. ACTH-(4–10) and ORG 2766 failed to influence active social contact, when administered 30 minutes before the test. The change in social contact by ACTH-(4–10) and ORG 2766 was not accompanied by an alteration in ambulation of the rats. It is concluded that ACTH-(4–10) and ORG 2766 decrease and increase respectively social interaction of pairs of rats. The expression of these effects however, depends on the test and treatment conditions and may be related to the action of brain-born ACTH-like peptides.