The divergent potency of antidepressants in the brain areas under study in the regulation of NLRP3 inflammasome activation may be partially explained by the fact that the hippocampus is a structure particularly sensitive to stressful stimuli and, in consequence, to neuroimmune modulation [5, 79], and may suggest the engagement of other pathways being responsible for the anti-inflammatory properties of antidepressant drugs in the frontal cortex in our model of depression. This evidence concerns the gene NLRP3 and major depressive disorder.