The role of mGlu5 in modulating consequences of chronic psychosocial stress using the CSC paradigm was investigated. Genetic ablation and pharmacological blockade of mGlu5 decreased the vulnerability to CSC-induced alterations. CSC exposure dysregulated hippocampal mGlu5 binding sites in wildtype mice. mGlu5 seems to be involved in chronic psychosocial stress-induced affective and somatic consequences.