Document Type
Article
Publication Date
6-1-2023
Original Citation
Tran T,
Monroy Hernandez C,
Nguyen H,
Wright S,
,
Tarantino L,
Chesler E,
Weinstock GM,
Zhou Y,
Bubier JA.
The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice. Genes Brain Behav. 2023;22(3):e12845.
Keywords
JGM, JMG, Mice, Male, Female, Animals, Cocaine, Collaborative Cross Mice, Mice, Inbred C57BL, Microbiota, Anti-Bacterial Agents
JAX Source
Genes Brain Behav. 2023;22(3):e12845.
ISSN
1601-183X
PMID
37114320
DOI
https://doi.org/10.1111/gbb.12845
Grant
This work was supported by NIDA (grant no. U01DA043809) to Jason A. Bubier, George Weinstock and Yanjiao Zhou and NIDA (grant no. GMW P50DA039841) to Elissa J. Chesler.
Abstract
The gut-brain axis is increasingly recognized as an important pathway involved in cocaine use disorder. Microbial products of the murine gut have been shown to affect striatal gene expression, and depletion of the microbiome by antibiotic treatment alters cocaine-induced behavioral sensitization in C57BL/6J male mice. Some reports suggest that cocaine-induced behavioral sensitization is correlated with drug self-administration behavior in mice. Here, we profile the composition of the naïve microbiome and its response to cocaine sensitization in two collaborative cross (CC) strains. These strains display extremely divergent behavioral responses to cocaine sensitization. A high-responding strain, CC004/TauUncJ (CC04), has a gut microbiome that contains a greater amount of Lactobacillus than the cocaine-nonresponsive strain CC041/TauUncJ (CC41). The gut microbiome of CC41 is characterized by an abundance of Eisenbergella, Robinsonella and Ruminococcus. In response to cocaine, CC04 has an increased Barnsiella population, while the gut microbiome of CC41 displays no significant changes. PICRUSt functional analysis of the functional potential of the gut microbiome in CC04 shows a significant number of potential gut-brain modules altered after exposure to cocaine, specifically those encoding for tryptophan synthesis, glutamine metabolism, and menaquinone synthesis (vitamin K2). Depletion of the microbiome by antibiotic treatment revealed an altered cocaine-sensitization response following antibiotics in female CC04 mice. Depleting the microbiome by antibiotic treatment in males revealed increased infusions for CC04 during a cocaine intravenous self-administration dose-response curve. Together these data suggest that genetic differences in cocaine-related behaviors may involve the microbiome.
Comments
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.