Gut Microbial Signals Influence Motivational Responses in the Male Mouse

Abstract

Mammalian motivation to obtain natural rewards is regulated by internal biological and external environmental factors. Increasing evidence suggests the gut microbiota may represent one such factor. Here, we observed that antibiotic (ABX)-induced disruption of the gut microbiota increased the motivation to obtain palatable rewards, elevated inflammatory cytokine levels and elicited significant alterations in synaptic plasticity-related gene pathways in the mouse nucleus accumbens (NAc). We also observed that the dynamic state of the gut microbiota partially impacts motivational responses and identified several gut microbial metabolites that could be driving this phenotype. Finally, surgical ablation of vagal signalling via subdiaphragmatic vagotomy partially rescued transcriptomic signatures in the NAc and elevations in inflammatory markers but was not enough to prevent the increase in motivational responses. Overall, our results highlight an important new role for the gut microbiota in regulating the cascade of metabolic, neurochemical and immunological events necessary for reward processing and motivation.