Involvement of neurotransmitters in the action of growth hormone-releasing hormone antagonist on passive avoidance learning.

The antagonist MZ-4-71 of growth hormone-releasing hormone (GH-RH) has been shown to suppress the secretion of GH and insulin-like growth factor-1 (IGF-1), suggesting that this class of analogs could be used for the therapy of disorders characterized by excessive GH secretion. Numerous GH-RH antagonists has been synthetized and shown to suppress the growth of various tumors. MZ-4-71 facilitates the consolidation of passive avoidance learning. Beta-amyloid 25-35 impairs the consolidation of passive avoidance learning and MZ-4-71 fully blocks this impairment. However, little is known about the possible mechanism of action of GR-RH antagonists on these actions. In the present work, the possible effects of different neurotransmitters on the action of MZ-4-71 were studied in the memory consolidation of passive avoidance behavior. The involvement of cholinergic, serotonergic, dopaminergic, GABA-ergic, adrenergic and opiate receptors was tested. Mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a nonselective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist, atropine, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline, or a nonselective opioid receptor antagonist, naloxone. Atropine, methysergide, cyproheptadine and naloxone prevented the effects of MZ-4-71 on passive avoidance learning, whereas haloperidol, phenoxybenzamine, propranolol and bicuculline did not change the effects of MZ-4-71. The results demonstrate that the muscarinic acetylcholine receptor, the 5-HT1/5-HT2 serotonergic receptor and opioid receptors are involved as mediators in the action of MZ-4-71 on the consolidation of passive avoidance learning.

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