Hippocampal GR- and CB1-mediated mGluR5 differentially produces susceptibility and resilience to acute and chronic mild stress in rats.

The molecular mechanism of individual response of susceptibility and resilience under psychological stress remains controversial and unclear. The present study aimed to explore the relationship of metabotropic glutamate receptor 5 (mGluR5) with glucocorticoid receptor (GR) or cannabinoid receptor (CB1) and further indicate the molecular mechanism of susceptibility and resilience to acute stress (AS) and chronic mild stress (CMS). Sucrose preference test and open field test were used to evaluate the response of susceptibility and resilience under stress in rats. The mRNA levels and protein expressions of mGluR5, GR, and CB1 were detected. AS induced a 35% reduction in the sucrose intake of rats, and these rats were considered as susceptible to stress; 21% of the rats showed resilience to the stress. Thirty-three percent of rats in the CMS group showed reduced sucrose water intake and were considered susceptible, while 20% of rats were considered resilient. Hippocampal mGluR5 mRNA and protein levels were increased in the susceptible rats. Pharmacological testing showed that GR was positively associated with mGluR5 in susceptible rats in the CMS group, while CB1 was negatively related to mGluR5 in susceptible rats in the AS group. The results suggested that GR and CB1 in the hippocampus might regulate mGluR5 protein and mRNA levels, which might be related to individual responses of susceptibility and resilience under AS and CMS.