Chronic or repeated exposure to stress in the form of trauma or major life events such as bereavement, prolonged conflict, or low socioeconomic status can promote the onset or development of stress-related psychiatric disorders in some, but not all, individuals. Thus, some individuals are more vulnerable to the adverse effects of stress while others are more resilient. One factor that promotes stress vulnerability is increased inflammatory processes1. We are also beginning to understand factors that promote stress resilience. The Bhatnagar Lab recently reported that a G- protein coupled receptor called sphingosine-1-phosphate receptor 3 (S1PR3) promotes stress resilience by mitigating stress-induced inflammation in the medial prefrontal cortex (mPFC). S1PR3 mRNA was also reduced in the blood of PTSD patients. In resilient rats, S1PR3 is increased by glucocorticoid receptors (GRs). To study the importance of GR-induced S1PR3, the Bhatnagar Lab developed a rat line in which the GR binding site near the S1PR3 gene is deleted (S1PR3GR-/GR- rats). These rats display anxiety-like behavior as assessed by the social interaction paradigm and increased peripheral inflammation as assessed by increased lymphocytes. However, effects of inflammatory processes in the mPFC are unknown.