Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses

Cuesta, Santiago; Burdisso, Paula; Segev, Amir; Kourrich, Saı̈d; Sperandio, Vanessa

doi:10.1016/j.chom.2022.09.014

Cited by 22 publications

(16 citation statements)

References 125 publications

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“…A similar reversible response was also reported for sensitization and CPP in response to morphine in male C57BL/6 mice 13 . Recently, treatment of male C57BL/6J mice with Proteobacteria was shown to alter cocaine neurobehavioral responses in a glycine dependent manner 14 . Finally, work in the alcohol field using the binge drinking model, drinking in the dark, using C57BL/6J mice given a 2‐week antibiotic pretreatment showed significantly increased alcohol consumption 15 ; which this increase could be reversed by sodium butyrate supplementation 16 .…”

Section: Introductionsupporting

confidence: 76%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran,

Monroy Hernandez,

Nguyen

et al. 2023

Genes Brain and Behavior

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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 selfadministration behavior in mice. Here, we profile the composition of the naïve micro-

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Section: Introductionsupporting

confidence: 76%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran,

Monroy Hernandez,

Nguyen

et al. 2023

Genes Brain and Behavior

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“…Lee and colleagues demonstrated that a shorter treatment with a different antibiotic cocktail led to a reduction in cocaine place preference at an intermediate dose 50 . Recent studies demonstrated production of gut microbiome-derived glycine can have marked effects on behavioral responses to cocaine 19 . Interesting recent work has even identified interactions between the microbiome and social stimuli in regulating cocaine place preference 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Robust literature indicates that connections between the brain and the gut microbiome modulate neuropsychiatric disease pathogenesis in animal models and clinical studies of autism, depression, anxiety, and substance use disorders 5,[8][9][10][11][12][13][14][15] . Indeed, previously published work demonstrates gut microbiome depletion results in significantly altered behavioral and transcriptional responses to cocaine and opioids 11,[16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

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Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking

Meckel

Simpson

Godino

et al. 2023

Preprint

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Cocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment. A growing body of research has detailed the important connections between the brain and the resident population of bacteria in the gut, the gut microbiome in psychiatric disease models. Acute depletion of gut bacteria results in enhanced reward in a mouse cocaine place preference model, and repletion of bacterially-derived short-chain fatty acid (SCFA) metabolites reverses this effect. However, the role of the gut microbiome and its metabolites in modulating cocaine-seeking behavior after prolonged abstinence is unknown. Given that relapse prevention is the most clinically challenging issue in treating substance use disorders, studies examining the effects of microbiome manipulations in relapse-relevant models are critical. Here, Sprague-Dawley rats received either untreated water or antibiotics to deplete the gut microbiome and its metabolites. Rats were trained to self-administer cocaine and subjected to either within-session threshold testing to evaluate motivation for cocaine or 21 days of abstinence followed by a cue-induced cocaine-seeking task to model relapse behavior. Microbiome depletion did not affect cocaine acquisition on an FR1 schedule. However, microbiome-depleted subjects exhibited significantly enhanced motivation for low dose cocaine on a within-session threshold task. Similarly, microbiome depletion increased cue-induced cocaine-seeking following prolonged abstinence. In the absence of a normal microbiome, repletion of bacterially-derived SCFA metabolites reversed the behavioral and transcriptional changes associated with microbiome depletion. These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.

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“…A similar reversible response was also reported for sensitization and CPP in response to morphine in male C57BL/6 mice. [13] Recently treatment of male C57BL/6J mice with Proteobacteria was shown to alter cocaine neurobehavioral responses in a glycine dependent manner[14].…”

Section: Introductionmentioning

confidence: 99%

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Tran

Hernandez

Nguyen

et al. 2022

Preprint

View full text Add to dashboard Cite

The gut microbiome-brain axis is increasingly recognized as an important pathway in regulation of cocaine addiction. Microbial products produced in 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. Cocaine-induced behavioral sensitization is correlated with drug self-administration behavior, therefore, is a predictor of addiction vulnerability. 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 ofLactobacillusthan the cocaine-nonresponsive strain CC041/TauUncJ (CC41). The gut microbiome of CC41 is characterized by an abundance ofEisenbergella, RobinsonellaandRuminococcus. In response to cocaine, CC04 has an increasedBarnsiellapopulation, 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 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 a sex-specific altered cocaine-sensitization response to antibiotics in female mice from CC04 that was not observed in male CC04 or either sex of CC41. Together these data suggest a complex relationship between host genetics, microbiome composition and cocaine sensitization behavior.FUNDINGU01DA043809 to JAB, GMW P50DA039841 to EJC

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Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses

Cited by 22 publications

References 125 publications

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking

The microbial community dynamics of cocaine sensitization in two behaviorally divergent strains of collaborative cross mice

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