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 30 min 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.
| Original language | English |
|---|---|
| Pages (from-to) | 155-158 |
| Number of pages | 4 |
| Journal | Behavioural Brain Research |
| Volume | 224 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 10 2011 |
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Keywords
- Antidepressive
- Anxiolytic actions
- GH-RH antagonist MZ-4-71
- Memory correction
ASJC Scopus subject areas
- Behavioral Neuroscience
Cite this
Effects of the growth hormone-releasing hormone (GH-RH) antagonist on brain functions in mice. / Telegdy, Gyula; Tanaka, Masaru; Schally, Andrew V.
In: Behavioural Brain Research, Vol. 224, No. 1, 10.10.2011, p. 155-158.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of the growth hormone-releasing hormone (GH-RH) antagonist on brain functions in mice
AU - Telegdy, Gyula
AU - Tanaka, Masaru
AU - Schally, Andrew V
PY - 2011/10/10
Y1 - 2011/10/10
N2 - 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 30 min 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.
AB - 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 30 min 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.
KW - Antidepressive
KW - Anxiolytic actions
KW - GH-RH antagonist MZ-4-71
KW - Memory correction
UR - http://www.scopus.com/inward/record.url?scp=79959558904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959558904&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2011.05.036
DO - 10.1016/j.bbr.2011.05.036
M3 - Article
C2 - 21672558
AN - SCOPUS:79959558904
VL - 224
SP - 155
EP - 158
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -