PT  - JOURNAL ARTICLE
AU  - Rebecca S. Hofford
AU  - Nicholas L. Mervosh
AU  - Tanner J. Euston
AU  - Katherine R. Meckel
AU  - Amon T. Orr
AU  - Drew D. Kiraly
TI  - The gut microbiome and its metabolites are necessary for morphine reward
AID  - 10.1101/2020.09.17.302570
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.17.302570
4099  - http://biorxiv.org/content/early/2020/09/19/2020.09.17.302570.short
4100  - http://biorxiv.org/content/early/2020/09/19/2020.09.17.302570.full
AB  - Recent evidence has demonstrated that the gut microbiome has marked effects on neuronal function and behavior. Disturbances to microbial populations within the gut have been linked to myriad models of neuropsychiatric disorders. However, the role of the microbiome in substance use disorders remains understudied. Here we show that animals with their gut microbiome depleted by non-absorbable antibiotics (Abx) exhibit decreased formation of morphine conditioned place preference and demonstrate marked changes in gene expression within the nucleus accumbens (NAc) in response to morphine. Replacement of short-chain fatty acid (SCFA) metabolites, which are reduced by microbiome knockdown, reversed the behavioral and transcriptional effects of microbiome depletion. This identifies SCFA as the crucial mediators of microbiome-brain communication responsible for the effects on morphine reward caused by microbiome knockdown. These studies add important new behavioral, molecular, and mechanistic insight to the role of gut-brain signaling in substance use disorders.Competing Interest StatementThe authors have declared no competing interest.