Antidepressant-like effects of urocortin 3 fragments

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-NH2. The results indicate that the total sequence of Ucn 3 is not necessary for the antidepressive action of Ucn 3. Furthermore, the antidepresant 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.