Effect of chronic stress on the lipopolysaccharide-induced activation of microglia in the ventral mesencephalon. Midbrain microglia were evaluated by immunohistochemistry with Iba-1 (left and middle columns) and OX-6 antibodies (right column) in vehicle-injected animals (A) through (F) and lipopolysaccharide (LPS)-injected animals (G) through (L) under nonstressed conditions ((A) through C) and (G) through (I)) and stressed conditions ((D) through (F) and (J) through (L)). Iba-1 immunohistochemistry is shown at low and high magnification (left and middle columns, respectively). (M) through (O) The effect of RU486 (mifepristone (11β-[p-(dimethylamino)phenyl]-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)) on the microglia population in response to LPS injection in stressed animals. Note that stress highly increased the microglial activation response to LPS injection (J) through (L) compared with nonstressed conditions (G) through (I). Note that, after LPS injection, most microglial cells display a round morphology typical of macrophages, whose density significantly increases under conditions of chronic stress. Also note how RU486 treatment strongly prevents the stress-induced sensitisation of microglia to subsequent LPS injection (M) through (O). The blue staining in all panels is the Monastral Blue inert tracer contained in the vehicle. Scale bars: 500 μm (A, D, G, J and M); 100 μm (all other panels). Abbreviations: V, Vehicle; S, Stress; SL, Lipopolysaccharide injected into stressed animals; SLR, Lipopolysaccharide injected into stressed animals treated with RU486.