Ethanol consumption following mild traumatic brain injury is related to blood-brain barrier permeability

Several preclinical and clinical studies that deal with the neuropathological consequences of mild traumatic brain injury (mTBI) have focused on unraveling its effect on ethanol drinking behavior. Previous reports describe changes in ethanol consumption, both in animal models of mTBI as well as in patients, after concussive brain injury. However, the neurobiological mechanisms underlying this phenomenon are still poorly understood. In the present study, we used a unique model of mouse lines divergently selected for high (HA) or low (LA) swim stress-induced analgesia to examine the effect of mTBI on ethanol drinking behavior. In comparison with LA mice, their HA counterparts exhibited increased blood-brain barrier (BBB) permeability, lower basal alcohol preference, and lower level of stress-induced ethanol intake. Here, we showed that mTBI attenuates voluntary ethanol intake in LA, but not in HA mice. Interestingly, BBB disruption after mannitol infusion also decreases the level of ethanol drinking behavior in this line. We conclude that in alcohol-preferring LA mice, BBB disruption as a consequence of mTBI attenuates ethanol consumption. Our results suggest that the innate level of BBB integrity plays a pivotal role in regulation of ethanol consumption in mice showing differential endogenous opioid system activity.