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The growth hormone-releasing hormone (GH-RH) antagonist MZ-4-71 has been shown to suppress secretion of GH and insulin-like growth factor-1 (IGF-1) secretion and to suppress the growth of various tumors.Little is known about the possible action of GR-RH antagonists on brain functions.We have shown that MZ-4-71 has antidepresssant-like effects in a modified forced swimming test (FST) in mice.In the present work an attempt is made to elucidate the possible mechanism of antidepressant action of MZ-4-71.The MZ-4-71 was synthesized in the laboratory of one of us (AV.Schally), and administered into the lateral ventricle in mice.The possible involvement of different transmitters was studied in a modified mouse forced swimming test (FST) by pretreating the animals with different receptor antagonist prior to MZ-4-71 administration.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 non-selective muscarinic acetylcholine receptor antagonist atropine, a D2, D3, D4 dopamine receptor antagonist haloperidol or a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist bicuculline, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist methysergide, a non-selective 5-HT2 serotonergic receptor antagonist cyproheptadine, Phenoxybenzamine, prazosin, methysergide, cyproheptadine and atropine prevented the effects of MZ-4-71 on the immobility, the climbing and the swimming times.Yohimbine, propranolol, haloperidol and bicuculline did not change the effects ofMZ-4-71.The results demonstrated that the antidepressant-like effects of MZ-4-71 in the modified mouse FST are mediated, at least in part, by an interaction of the α1-adrenergic, 5-HT1/5-HT2 serotonergic, and muscarinic acetylcholine receptors.