Neurotransmitter-mediated action of an antagonist of growth hormone-releasing hormone on anxiolysis in mice

Antagonists of growth hormone-releasing hormone (GH-RH), such as MZ-4-71 suppress the secretion of GH. These findings suggest that GH-RH antagonists could be used for the therapy of disorders characterized by excessive GH secretion. It has been also demonstrated that MZ-4-71 displays antidepressant effects in a modified forced swimming test in mice, exerts anxiolytic effects in an elevated plus maze test, improves memory consolidation in passive avoidance learning, and corrects the impairment of memory consolidation caused by β-amyloid (25-35) in mice. However, little is known about the mechanisms of action of MZ-4-71 on brain functions. In the present work, the involvement of the adrenergic, serotonergic and GABA-ergic receptors in the anxiolytic action of MZ-4-71 was studied in an elevated plus maze. Mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, an α1/α2β-adrenergic receptor antagonist, prazosin, an α2-adrenergic receptor antagonist, yohimbine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, and a γ-aminobutyric acid subunit (GABA-A) receptor antagonist, bicuculline. Phenoxybenzamine, prazosin, yohimbine, methysergide, cyproheptadine and bicuculline prevented the effects of MZ-4-71 on the elevated plus maze revealing that the anxiolytic actions of MZ-4-71 in this test are mediated, at least in part, by the an interaction of the α1/α2-adrenergic, 5-HT1/5-HT2 serotonergic and GABA-A-ergic receptors.