The Effects of Depleted Peripheral Macrophages on Alcohol Addiction Reward-Seeking Behaviors in Mice

Alcohol addiction is a global issue negatively affecting both mental and physical health. Although previous data suggests a relationship between alcohol and immunity, significant gaps in knowledge remain in exploring how specific functions of the immune system contribute to the formation of addiction memories. This thesis explores shifts in DSM diagnostic criteria, brain regions beyond the canonical dopamine reward circuitry such as the hippocampus, and the importance of female representation in alcohol addiction research. Previous data suggest stress and weaker immune systems playing a role in addiction vulnerability. Motivated by these findings, we hypothesize that suppressing innate immune components will lead to a higher risk of addiction formation. To confirm this, liposomal clodronate was administered to the mice depleting macrophage function and systemically modifying inflammatory responses. The behavioral aspect of the investigation was completed using a four-day drinking paradigm called Drinking in the Dark (DID) helping assess binge drinking behaviors, while the Ethanol Conditioned Place Preference (eCPP) evaluated reward-seeking behaviors. Neither of the paradigms revealed a statistically significant relationship but showed variability often observed in humans consuming alcohol. The molecular analysis of this investigation was completed by performing a blood cytokine analysis and examining neuronal activation of the hippocampus using cFos immunohistochemistry (IHC). The cFos suggested a potential aversive relationship between innate immunity depletion and alcohol consumption, though additional research is essential to fully understand this relationship. These results have a goal of helping us to understand the effects of inflammation through depletion of peripheral macrophages on alcohol related behaviors and context associations.