80. Minocycline attenuates stress-induced changes in leukocyte activation and anxiety-like behavior

Abstract

Repeated social defeat (RSD) is a murine stress model that recapitulates many key behavioral, immunological, and physiological changes observed in humans exposed to psychological stressors. Exposure to RSD increases circulating monocytes, macrophage recruitment to the brain, and activation of microglia, resulting in an increase in anxiety-like behavior. Minocycline is an antibiotic that readily crosses the blood–brain-barrier and has anti-inflammatory properties, down regulating microglial pro-inflammatory cytokine output within the central nervous system. Thus, the objective of this study was to determine if suppressing microglia activation with minocycline prevents the RSD-induced alterations in immune function and anxiety-like behavior. In these experiments, daily oral administration of minocycline was given to C57bl/6 mice beginning two days prior to RSD. Here we show that minocycline attenuated RSD-induced alterations in myeloid cell trafficking, macrophage re-distribution and anxiety-like behavior. For example, minocycline prevented stress-induced increases in macrophage trafficking to the brain. In addition, mice treated with minocycline did not have stress-induced increases in circulating leukocytes or splenomegaly. Activation of circulating monocytes and granulocytes by RSD was also attenuated by minocycline. Furthermore, minocycline pretreatment blocked the induction of anxiety-like behavior after RSD. Collectively these data indicate that minocycline ameliorates stress-induced anxiety-like behavior by attenuating cellular redistribution and activation in the periphery and macrophage trafficking to the brain. Grants: R01MH097243-02 R01MH093473-03.