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: Gyula Telegdy, Masaru Tanaka, Andrew V Schally
• Journal: Behavioural brain research (Behav Brain Res) Vol. 224 Issue 1 Pg. 155-8 (Oct 10 2011) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 21672558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier B.V.

Chemical References

• Amyloid beta-Peptides
• MZ 4-71
• Peptide Fragments
• amyloid beta-protein (25-35)
• Sermorelin
• Growth Hormone-Releasing Hormone

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Avoidance Learning (drug effects)
• Behavior, Animal (drug effects)
• Brain (drug effects, physiology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Exploratory Behavior (drug effects)
• Growth Hormone-Releasing Hormone (antagonists & inhibitors)
• Male
• Maze Learning (drug effects)
• Mice
• Peptide Fragments (pharmacology)
• Sermorelin (analogs & derivatives, pharmacology)
• Swimming (psychology)