The Function Role Of Metabotropic Glutamate Receptors Within The MPFC In Stress Susceptibility And Resilience

Resilience or susceptibility to aversive events has a central role in determining the etiology of some stress-related psychiatric disorders such as depression.At present,the research on neurobiological mechanisms underlying stress susceptibility and resilience is limited and there are many unknowns.In this study,we first investigated the related brain structures involved in stress susceptibility and resilience by using chronic social defeat stress(CSDS)model in adult male wild house mice.We found that: 1.about 39.1% of mice showed depression-like behaviors when exposed to CSDS;2.c-Fos expressions,a marker of neuron activity,showed obvious differences in the medial prefrontal cortex(m PFC),hypothalamus paraventricular nucleus,medial amygdala and the lateral habenular nucleus among the control,stress resilence and susceptibility groups of mice;3.serum corticosterone levels were significantly higher in susceptible group compared with resilience groups.As glutamate system play an essential role in a series of mental disorders,we then further investigated the function role of metabotropic glutamate receptors in the stress "susceptibility / resilience" which focused primar on different subregions of the m PFC in C57 adult male mice.Our results showed that: 1.approximately 51.6% of the C57 mice exhibited depression-or anxiety-like behaviors after exposure to CSDS;2.when a susceptible C57 mice was confronted with a social stressor,c-Fos expression in the prelimbic cortex(Pr L)subregion of the m PFC substantially increased;3.compared with the resilient and control groups,the expression of m Glu2/3 elevated in the Pr L of the susceptible group.The expression of m Glu5 showed no significant difference among the three groups in the whole m PFC;and 4.pharmacology study results showed that the social avoidance symptoms of the susceptible mice could be rapidly relieved by intra-Pr L administration of LY341495—an m Glu R2/3 antagonists.Taken together,our study showed that mice could be divided into“susceptibility” or “resilience” subtypes when exposure to CSDS and m Glu2/3 in the Pr L may play an important regulatory role in stress vulnerability.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.