Oxytocin reverses ethanol consumption and neuroinflammation induced by social defeat in male mice.

Oxytocin (OXT) modulates social interactions, attenuates stressful responses and can decrease drug-seeking and taking behaviors. In previous studies, we observed that social defeat (SD) induced a long-lasting increase in ethanol intake and neuroinflammation in male mice. We also know that OXT blocks the increase in cocaine reward induced by SD. Therefore, in the present study we aimed to evaluate the effect of 1 mg/kg of OXT administered 30 min before each episode of SD on ethanol consumption and the neuroinflammatory response in adult male mice. Three weeks after the last SD, mice underwent oral ethanol self-administration (SA) procedure, and striatal levels of the two chemokines CX3CL1 and CXCL12 were measured after the last SD and at the end of the ethanol SA. OXT administration blocked the increase in voluntary ethanol consumption observed in defeated mice, although it did not affect motivation for ethanol. An increase in the striatal levels of CX3CL1 and CXCL12 was observed in defeated animals immediately after the last defeat and after the ethanol SA. However, defeated mice treated with OXT did not show this increase in the neuroinflammatory response. In conclusion, OXT treatment can be a powerful therapeutic target to reduce the negative effects of social stress on ethanol consumption and the neuroinflammatory process.