Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors.
The role of brain corticotropin-releasing factor type 2 (CRF2) receptors in behavioral stress responses remains controversial. Conflicting findings suggest pro-stress, anti-stress or no effects of impeding CRF2 signaling. Previous studies have used antisauvagine-30 as a selective CRF2 antagonist. Th...
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doaj-cca0bac2122b4ee8af9da47e197136782020-11-25T00:43:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e6394210.1371/journal.pone.0063942Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors.Eric P ZorrillaAmanda J RobertsJean E RivierGeorge F KoobThe role of brain corticotropin-releasing factor type 2 (CRF2) receptors in behavioral stress responses remains controversial. Conflicting findings suggest pro-stress, anti-stress or no effects of impeding CRF2 signaling. Previous studies have used antisauvagine-30 as a selective CRF2 antagonist. The present study tested the hypotheses that 1) potential anxiolytic-like actions of intracerebroventricular (i.c.v.) administration of antisauvagine-30 also are present in mice lacking CRF2 receptors and 2) potential anxiolytic-like effects of antisauvagine-30 are not shared by the more selective CRF2 antagonist astressin2-B. Cannulated, male CRF2 receptor knockout (n = 22) and wildtype littermate mice (n = 21) backcrossed onto a C57BL/6J genetic background were tested in the marble burying, elevated plus-maze, and shock-induced freezing tests following pretreatment (i.c.v.) with vehicle, antisauvagine-30 or astressin2-B. Antisauvagine-30 reduced shock-induced freezing equally in wildtype and CRF2 knockout mice. In contrast, neither astressin2-B nor CRF2 genotype influenced shock-induced freezing. Neither CRF antagonist nor CRF2 genotype influenced anxiety-like behavior in the plus-maze or marble burying tests. A literature review showed that the typical antisauvagine-30 concentration infused in previous intracranial studies (∼1 mM) was 3 orders greater than its IC50 to block CRF1-mediated cAMP responses and 4 orders greater than its binding constants (Kd , Ki ) for CRF1 receptors. Thus, increasing, previously used doses of antisauvagine-30 also exert non-CRF2-mediated effects, perhaps via CRF1. The results do not support the hypothesis that brain CRF2 receptors tonically promote anxiogenic-like behavior. Utilization of CRF2 antagonists, such as astressin2-B, at doses that are more subtype-selective, can better clarify the significance of brain CRF2 systems in stress-related behavior.http://europepmc.org/articles/PMC3756045?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eric P Zorrilla Amanda J Roberts Jean E Rivier George F Koob |
spellingShingle |
Eric P Zorrilla Amanda J Roberts Jean E Rivier George F Koob Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. PLoS ONE |
author_facet |
Eric P Zorrilla Amanda J Roberts Jean E Rivier George F Koob |
author_sort |
Eric P Zorrilla |
title |
Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. |
title_short |
Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. |
title_full |
Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. |
title_fullStr |
Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. |
title_full_unstemmed |
Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2 receptors. |
title_sort |
anxiolytic-like effects of antisauvagine-30 in mice are not mediated by crf2 receptors. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
The role of brain corticotropin-releasing factor type 2 (CRF2) receptors in behavioral stress responses remains controversial. Conflicting findings suggest pro-stress, anti-stress or no effects of impeding CRF2 signaling. Previous studies have used antisauvagine-30 as a selective CRF2 antagonist. The present study tested the hypotheses that 1) potential anxiolytic-like actions of intracerebroventricular (i.c.v.) administration of antisauvagine-30 also are present in mice lacking CRF2 receptors and 2) potential anxiolytic-like effects of antisauvagine-30 are not shared by the more selective CRF2 antagonist astressin2-B. Cannulated, male CRF2 receptor knockout (n = 22) and wildtype littermate mice (n = 21) backcrossed onto a C57BL/6J genetic background were tested in the marble burying, elevated plus-maze, and shock-induced freezing tests following pretreatment (i.c.v.) with vehicle, antisauvagine-30 or astressin2-B. Antisauvagine-30 reduced shock-induced freezing equally in wildtype and CRF2 knockout mice. In contrast, neither astressin2-B nor CRF2 genotype influenced shock-induced freezing. Neither CRF antagonist nor CRF2 genotype influenced anxiety-like behavior in the plus-maze or marble burying tests. A literature review showed that the typical antisauvagine-30 concentration infused in previous intracranial studies (∼1 mM) was 3 orders greater than its IC50 to block CRF1-mediated cAMP responses and 4 orders greater than its binding constants (Kd , Ki ) for CRF1 receptors. Thus, increasing, previously used doses of antisauvagine-30 also exert non-CRF2-mediated effects, perhaps via CRF1. The results do not support the hypothesis that brain CRF2 receptors tonically promote anxiogenic-like behavior. Utilization of CRF2 antagonists, such as astressin2-B, at doses that are more subtype-selective, can better clarify the significance of brain CRF2 systems in stress-related behavior. |
url |
http://europepmc.org/articles/PMC3756045?pdf=render |
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