The gut microbiota alone and in combination with a social stimulus regulates cocaine reward in the mouse

The gut microbiota is a key factor in the maintenance of physiological homeostasis and immunity. Correlational studies have demonstrated that alterations in microbiota composition have been associated with addiction. Moreover, animal studies have confirmed a link between reward and social processes, which may be shaped by the gut microbiota thus influencing neurodevelopment and the programming of social behaviors across diverse animal species. However, whether there is an interaction between the microbiota and social reward processes in the context of drug reward remains unclear. To this end, we explored the influence of gut microbiota in regulating behaviourally conditioned responses to different rewards (cocaine and social interactions). Depletion of the intestinal microbiota resulted in differential reward responses to both drug and social stimuli with an attenuation of the former and enhancement of the latter independent of concomitant immune changes. Moreover, the combination of depleting the gut microbiota in the presence of a positive social stimulus attenuates cocaine reward. Together these data suggest that the two-pronged approach of targeting the microbiota and enhancing social behaviour could constitute a valuable component in reducing harm in drug use by altering the salient effects of cocaine.

Automated summary

The gut microbiota plays a crucial role in maintaining physiological balance and immunity, and is associated with addiction. Animal studies have shown a link between reward and social processes, which can be influenced by the gut microbiota, impacting neurodevelopment and social behaviors across different species. Depletion of the gut microbiota alters reward responses to drug and social stimuli, with a decrease in drug reward and an increase in social reward. Additionally, depleting the gut microbiota in the presence of positive social stimuli attenuates cocaine reward. These findings suggest that targeting the microbiota and enhancing social behavior could be beneficial in reducing harm from drug use.