Relief from detrimental consequences of chronic psychosocial stress in mice deficient for the metabotropic glutamate receptor subtype 7.

Chronic stress-related psychiatric conditions and comorbid somatic pathologies are an enormous public health concern in modern society. The etiology of these disorders is complex, with stressors holding a chronic and psychosocial component representing the most acknowledged risk factor. During the last decades, research on the metabotropic glutamate receptor (mGlu) system advanced dramatically and much attention was given to the role of the metabotropic glutamate receptor subtype 7 (mGlu7) in acute stress-related behavior and physiology. However, virtually nothing is known about the potential involvement of mGlu7 in chronic psychosocial stress-related conditions. Using the chronic subordinate colony housing (CSC, 19 days) in male mice, we addressed whether central mGlu7 is altered upon chronic psychosocial stressor exposure and whether genetic ablation of mGlu7 interferes with the multitude of chronic stress-induced alterations. CSC exposure resulted in a downregulation of mGlu7 mRNA transcript levels in the prefrontal cortex, a brain region relevant for stress-related behaviors and physiology. Interestingly, mGlu7 deficiency relieved multiple chronic stress-induced alterations including the CSC-induced anxiety-prone phenotype; mGlu7 ablation also ameliorated CSC-induced physiological and immunological consequences such as hypothalamo-pituitary-adrenal (HPA) axis dysfunctions and colonic inflammation, respectively. Together, our findings provide first evidence for the involvement of mGlu7 in a wide range of behavioral and physiological alterations in response to chronic psychosocial stressor exposure. Moreover, the stress-protective phenotype of genetic mGlu7 ablation suggests mGlu7 pharmacological blockade to be a relevant option for the treatment of chronic stress-related emotional and somatic dysfunctions. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.