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mGlu2/3 receptor in the prelimbic cortex is implicated in stress resilience and vulnerability in mice.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2021 Sep 05; Vol. 906, pp. 174231. Date of Electronic Publication: 2021 Jun 04. - Publication Year :
- 2021
-
Abstract
- Resilience, referring to "achieving a positive outcome in the face of adversity", is a common phenomenon in daily life. Elucidating the mechanisms of stress resilience is instrumental to developing more effective treatments for stress-related psychiatric disorders such as depression. Metabotropic glutamate receptors (mGlu2/3 and mGlu5) within the medial prefrontal cortex (mPFC) have been recently recognized as promising therapeutic targets for rapid-acting antidepressant treatment. In this study, we assessed the functional roles of the mGlu2/3 and mGlu5 within different subregions of the mPFC in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in mice. Our results showed that approximately 51.6% of the subjects exhibited depression- or anxiety-like behaviors after exposure to CSDS. When a susceptible mouse was confronted with an attacker, c-Fos expression in the prelimbic cortex (PrL) subregion of the mPFC substantially increased. Compared with the resilient and control groups, the expression of mGlu2/3 was elevated in the PrL of the susceptible group. The expression of mGlu5 showed no significant difference among the three groups in the whole mPFC. Finally, we found that the social avoidance symptoms of the susceptible mice were rapidly relieved by intra-PrL administration of LY341495-an mGluR2/3 antagonists. The above results indicate that mGluR2/3 within the PrL may play an important regulatory role in stress-related psychiatric disorders. Our results are meaningful, as they expand our understanding of stress resilience and vulnerability which may open an avenue to develop novel, personalized approaches to mitigate depression and promote stress resilience.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acids pharmacology
Amino Acids therapeutic use
Animals
Depression etiology
Depression prevention & control
Depression psychology
Disease Models, Animal
Humans
Male
Mice
Prefrontal Cortex drug effects
Prefrontal Cortex metabolism
Receptors, Metabotropic Glutamate antagonists & inhibitors
Resilience, Psychological drug effects
Social Defeat
Stress, Psychological drug therapy
Stress, Psychological etiology
Stress, Psychological psychology
Xanthenes pharmacology
Xanthenes therapeutic use
Depression pathology
Prefrontal Cortex pathology
Receptors, Metabotropic Glutamate metabolism
Stress, Psychological pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 906
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34090896
- Full Text :
- https://doi.org/10.1016/j.ejphar.2021.174231