In this study we find that depletion of the gut microbiota results in a marked change in behavioral responses to cocaine in multiple paradigms. This suggests that interactions along the gut-brain access are important for development of cocaine reward associations as well as sensitized behavioral responses to cocaine. While the mechanistic underpinnings that are responsible for these behavioral changes are not fully clear, we found that depletion of gut bacteria resulted in altered transcriptional profiling in the NAc, an important area for the development of both place preference and locomotor sensitization. Together these data provide important insights into the addiction process as well as provides novel targets for potential treatment interventions to improve treatment outcomes in drug addicted individuals.
