The effects of the urocortins on the hypothalamic-pituitary-adrenal axis - similarities and discordancies between rats and mice.

The urocortins (Ucn I, Ucn II and Ucn III) are structural analogues of corticotropin-releasing factor (CRF). The aim of our present experiments was to compare the effects of the urocortins on the hypothalamic-pituitary-adrenal (HPA) axis in rats and mice, including the hypothalamic adrenocorticotropic hormone (ACTH) secretagogues, such as CRF and arginine vasopressin (AVP). Therefore, male CFLP mice and male Wistar rats were injected intracerebroventricularly (icv) with 0.5, 1, 2 and 5 µg/2 µl of Ucn I, Ucn II or Ucn III. After 30 min the animals were decapitated, and then, hypothalamic CRF and AVP concentrations and plasma ACTH and corticosterone (CORT) levels were measured. All measurements were performed by enzyme-linked immunosorbent assays (ELISA), except that of the plasma CORT level, which was determined by chemofluorescent assay. Ucn I increased significantly the hypothalamic CRF and AVP concentrations in both rats and mice. Ucn II and Ucn III influenced significantly only the hypothalamic CRF concentration in rats, without affecting the hypothalamic AVP concentration. In contrast, Ucn II and Ucn III increased significantly only the hypothalamic AVP concentration in mice, without affecting the hypothalamic CRF concentration. The hypothalamic changes were reflected more or less accurately by changes of the plasma ACTH and CORT levels. The present experiments demonstrate that the urocortins regulate the HPA axis centrally via modulation of the hypothalamic ACTH secretagogues and that there are some similarities and discordancies between rats and mice regarding this regulation.

The effects of CRF and urocortins on the sociability of mice.

The aim of our study was to determine the role of corticotropin-releasing factor (CRF), the urocortins (Ucn1, Ucn2 and Ucn3) and their receptors (CRF1 and CRF2) in the sociability of mice. Male CFLP mice were administered intracerebroventricularly (icv) with CRF and urocortins alone or in combination with antalarmin (specific CRF1 antagonist) and astressin2B (specific CRF2 antagonist) and then investigated in a Crawley social interaction test arena, that consists of three chambers. An unknown male in a cage was put in the first chamber and an empty cage was put in the opposite chamber. The tested male was habituated with the middle chamber for 5min and then allowed to explore the remaining chambers for 5min, during which the number of entries and the time of interaction were measured. Intracerebroventricular administration of CRF decreased significantly the number of entries and the time of interaction with the unknown male and these effects were blocked by antalarmin, but not astressin2B. In contrast, central administration of Ucn1 increased significantly the number of entries into the chamber of the unknown male, without changing the time of interaction and this effect was blocked by astressin2B, but not antalarmin. Central administration of Ucn2 and Ucn3 didn't influence remarkably the number of entries, but it reduced the time of interaction between the male mice. Our study suggests that CRF and Ucn1 may play important, but different roles in sociability, and that Ucn2 and Ucn3, playing similar roles, must be also involved in social interactions.

The effects of CRF and urocortins on the preference for social novelty of mice.

The aim of the present study was to determine the role of corticotropin-releasing factor (CRF), the urocortins (UCN 1, UCN 2 and UCN 3) and their receptors (CRF1 and CRF2) in the preference for social novelty of mice. Male CFLP mice were administered intracerebroventricularly (ICV) with CRF, UCN 1, UCN 2 or UCN 3 and/or antalarmin or astressin 2B, selective antagonists of CRF1 receptor and CRF2 receptor, respectively. The mice were investigated in a Crawley social interaction test arena consisting of three chambers: an unknown female was set in the first chamber and a known female, with which the male was familiarized previously for 24h, was set in the third chamber. First the tested male was habituated with the middle chamber for 5min and then allowed to explore the remaining chambers for 5min, during which the number of entries and the time of interaction were measured. CRF decreased significantly the number of entries and the time of interaction with the unknown female, but not the known female. UCN 1 decreased significantly the number of entries into the chamber of the unknown female, but not the known female, without changing the time of interaction. All decreasing effects were reversed by antalarmin, but not astressin 2B. UCN 2 and UCN 3 didn't influence significantly any of the parameters. The present study suggests that CRF and UCN 1 decrease the preference for social novelty by activating CRF1 receptor, while UCN 2 and UCN 3, activating selectively CRF2 receptor, do not participate to male-female interaction.