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

• Depletion of the gut microbiota altered reward responses to both cocaine and social stimuli. • The combination of depleting the gut microbiota in the presence of social stimulus attenuates cocaine reward. • Reductions in proinflammatory cytokines in the ileum of animals with a depleted microbiota may modulate brain reward responses. 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. [ABSTRACT FROM AUTHOR]