Neurotransmissions of antidepressant-like effects of neuromedin U-23 in mice.
Neuromedin U (NmU) is a widely distributed and multifunctional peptide in the central nervous system and the peripheral tissues. Little is know about the mechanisms of NmU on brain functions. The rodent isoform of the NmU, NmU-23, has been shown to have anxiolytic effects involved in the β-adrenergic and cholinergic nervous systems in elevated plus maze test. NmU-23 was tested for antidepressant-like effects in modified forced swimming test (FST) in mice and furthermore, the involvement of the adrenergic, serotonergic, cholinergic, dopaminergic or gaba-ergic receptors in the antidepressant-like effect of NmU-23 was studied in modified mice FST. Mice were pretreated with a non-selective α-adrenergic receptor antagonist phenoxybenzamine, an α1/α2β-adrenergic receptor antagonist, prazosin, an α2-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, nonselective muscarinic acetylcholine receptor antagonist, atropine, D2,D3,D4 dopamine receptor antagonist, haloperidol or γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline. NmU-23 showed the antidepressant-like effects by decreasing the immobility time and increasing the climbing and swimming time. Prazosin, haloperidol, and bicuculline prevented the effects of NmU-23 on the climbing and swimming time. Methysergide and cyproheptadine prevented the effects of NmU-23 on the immobility, swimming and climbing time. Atropine prevented the effects of NmU-23 on the climbing time. Phenoxybenzamine, yohimbine and propranolol did not change the effects of NmU-23. The results demonstrated that the antidepressant-like effect of NmU-23 is mediated, at least in part, by an interaction of the α2-adrenergic, 5-HT1-2 serotonergic, D2,D3,D4 dopamine receptor, muscarinic acetylcholine receptors and γ-aminobutyric acid subunit A (GABAA) receptor in a modified mouse FST.
Department of Pathophysiology, MTA-SZTE Neuroscience Research Group, Faculty of Medicine, University of Szeged, Semmelweis 1, 6701 Szeged, Hungary.
Masaru
M
Tanaka
Department of Pathophysiology, MTA-SZTE Neuroscience Research Group, Faculty of Medicine, University of Szeged, Semmelweis 1, 6701 Szeged, Hungary. Electronic address: telegdy@patph.szote.u-szeged.hu.
Gyula
G
Telegdy
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009479:Neuropeptides / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects*
D000928:Antidepressive Agents; D058787:GABA-A Receptor Antagonists; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D012702:Serotonin Antagonists; C056900:neuromedin U; D001285:Atropine; D008784:Methysergide; D001640:Bicuculline
Depression; Neuromedin U; Receptor