Interestingly, in a non-inflammatory context, the lack of EP4 signaling is associated with increased depression-like behavior [59], suggesting that this receptor could play a role in emotional behavior, as it has been described for other prostaglandin receptors (EP2, EP3) which also mediate the prostaglandin effect on synaptic plasticity in the spinal cord [60]. This evidence concerns the gene PTGER3 and depressive disorder.