Antidepressant-like effects of urocortin 3 fragments

Abstract

Urocortin 3 (Ucn 3) and various Ucn 3 fragments were tested with regard to antidepressive action in a modified forced swimming test following icv administration to mice. The fragment Ucn 3 (34-36) proved ineffective, whereas Ucn 3 (18-38), Ucn 3 (19-27), Ucn 3 (28-38), Ucn 3 (34-38), and Ucn 3 (36-38) demonstrated antidepressive-like action by shortening the immobility time and increasing the climbing and swimming times. The shortest molecule which elicited most of the antidepressive effects was the tripeptide Ucn 3 (36-38), H-Ala-Gln-Ile-NH(2). The results indicate that the total sequence of Ucn 3 is not necessary for the antidepressive action of Ucn 3. Furthermore, the antidepressant actions of Unc3 (19-27) and Ucn 3 (36-38) can be blocked by the CRF2 receptor antagonist Astressin 2β. Establishment of the smallest active sequence of the molecule may allow the synthesis of analogs or mimetics for antidepressive drugs.