Involvement of adrenergic and serotonergic receptors in antidepressant-like effect of urocortin 3 in a modified forced swimming test in mice.
Most of the evidence suggests that peptides in the corticotropin-releasing factor (CRF) family act on CRF receptors and are involved in depressive disorders. Urocortin 3 (Ucn 3) is specific for CRF type 2 (CRF(2)) receptors and mediates anxiolytic-like action. Little is known about the roles of Ucn 3 and CRH(2) receptors on depressive disorders. The previous study revealed that Ucn 3 elicits the antidepressant-like action by shortening the immobility time and increasing both the climbing time and the swimming time. The involvement of the adrenergic and serotonergic receptors in the antidepressant-like effect of Ucn 3 (0.5μg/2μl, i.c.v.) was studied in a modified forced swimming test (FST) in mice. Mice were pretreated with a non-selective α-adrenergic receptor antagonist, phenoxybenzamine, an α(1)/α(2β)-adrenergic receptor antagonist, prazosin, an α(2)-adrenergic receptor antagonist, yohimbine, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist, methysergide, a non-selective 5-HT(2) serotonergic receptor antagonist, cyproheptadine or a β-adrenergic receptor antagonist, propranolol. Phenoxybenzamine prevented the effects of Ucn 3 on the immobility time. Prazosin prevented the effects of Ucn 3 on the climbing time. Yohimbine prevented the effects of Ucn 3 on the immobility, climbing and swimming times. Methysergide prevented the effects of Ucn 3 on the immobility and climbing time. Cyproheptadine prevented the effects of Ucn 3 on the swimming time. Propranolol did not change the effects of Ucn 3. The results demonstrated that the antidepressant-like effect of Ucn 3 is mediated, at least in part, by an interaction of the α-adrenergic and serotonergic receptors in a modified mouse FST.
Tanaka
Masaru
M
Institute of Pathophysiology, University of Szeged, Semmelweis u 1, Szeged H-6701, Hungary.
Telegdy
Gyula
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009483:Neuropsychological Tests; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming; D054832:Urocortins / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D054832:Urocortins