Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice.
Most of the evidence suggests that corticotropin-releasing hormone (CRH) is involved in mood disorders. The CRF receptors type 1 (CRF(1) receptors) elicit a stress response, and their natural and synthetic antagonists have been studied as possible drugs against depression, whereas CRF receptors type 2 (CRF(2) receptors) appear to alleviate the stress response and mediate anxiolytic action. Other CRF family peptides are urocortin 1 (Ucn 1), urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3). Little is known about the action of Ucn 1, Ucn 2 and Ucn 3 on depressive disorders. Antidepressant-like effects of Ucn 1, Ucn 2 and Ucn 3 (0.13, 0.25 and 0.5 microg/2 microl, i.c.v.) were assayed in mice in a modified forced swimming test (FST). This modified FST predicts the clinical efficacy of an antidepressant drug through the scoring of immobility, climbing and swimming behavior. The study demonstrated that Ucn 1 had no action on any of parameters studied in the modified FST. Ucn 2 elicited antidepressive-like action by shortening the immobility time. Additionally Ucn 2 significantly increased the climbing and swimming times. Ucn 3 likewise displayed an antidepressive-like effect by shortening the immobility time, and increasing the climbing and swimming times. The results suggest that CRF(2) receptor stimulation by Ucn 2 or Ucn 3 leads to antidepressant-like action, but dual stimulation of the CRF(1) and CRF(2) receptors by Ucn 1 does not trigger antidepressant-like action in the modified mouse FST.
Tanaka
Masaru
M
Institute of Pathophysiology, University of Szeged, Semmelweis u. 1, H-6701 Szeged, Hungary.
Telegdy
Gyula
G
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D046353:Immobility Response, Tonic / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D051381:Rats; D013550:Swimming; D054832:Urocortins / Q000627:therapeutic use*
D000928:Antidepressive Agents; D054832:Urocortins