title: Effects of the growth hormone-releasing hormone (GH-RH) antagonist on brain functions in mice.
abstract: 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. These findings suggested that GH-RH antagonists could be used for the therapy of disorders characterized by excessive GH secretion. A number of GH-RH antagonists has been synthesized, and shown to suppress the growth of various tumors. However, little is known about the possible action of GR-RH antagonists on brain functions. In the present work, the influence of MZ-4-71 on different aspects of brain function was studied in mice, following its administration into the lateral brain ventricle. The effects tested included the action of MZ-4-71 on passive avoidance learning and on the impairment of the consolidation of a passive avoidance reflex caused by beta-amyloid 25-35, antidepressive action in a forced swimming test, and anxiolytic action on plus-maze and open-field behavior. MZ-4-71 facilitated the consolidation of passive avoidance learning. Beta-amyloid 25-35 administered immediately after the learning trial impaired the consolidation of passive avoidance learning. MZ-4-71 fully blocked this impairment when given simultaneously with or 30min following beta-amyloid 25-35 administration icv. In the forced swimming tests, MZ-47-1 demonstrated antidepressive-like action and in the plus-maze, depending on the dose used it elicited mild anxiolytic action, however, in open-field behavior tests, it displayed no action on locomotion, rearing or grooming. The results demonstrate that MZ-4-71 affects the brain functions: by improving memory consolidation in passive avoidance learning and correcting the impairment of the memory consolidation caused by beta-amyloid 25-35. MZ-4-71 also elicits anxiolytic and antidepressive effects, but it does not influence the open-field activity. Further experimental work with MZ-4-71 is necessary, to determine the possible mechanism of action. The results imply a possible merit of a clinical trial with MZ-4-71 in patients with anxiety, depression and cognitive impairment, as observed in Alzheimer's disease.
authors.affiliation: Department of Pathophysiology, University of Szeged, Hungary. telegdy@patph.szote.u-szeged.hu
authors.forename: Gyula
authors.initials: G
authors.lastname: Telegdy
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013550:Swimming / Q000523:psychology
chemical_list: D016229:Amyloid beta-Peptides; C095215:MZ 4-71; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone