We tested this hypothesis by assessing anxiety-like and depression-like behavior in defeated rats following no knock-down (iAAV-scramble), knock-down of S1PR3 alone (cocktail of iAAV-S1PR3 and iAAV-scramble), knock-down of S1PR3 and TNFα (cocktail of iAAV-S1PR3 and iAAV- TNFα), or knock-down of S1PR3 and IL1β (iAAV-S1PR3 and iAAV-IL1β). Here, S1PR3 is linked to major depressive disorder.