How gut bacteria influence the effects of cocaine in mice

How gut bacteria influence the effects of cocaine in mice

Summary: Cocaine use supports the growth of γ-proteobacteria, a common gut bacteria that consumes glycine. As glycine levels decrease, mouse models show a greater response to cocaine with abnormal behaviors including increased drug-induced locomotion and drug-seeking behavior.

Source: Cell Press

Common gut bacteria can enhance the effects of cocaine in mice, researchers report Nov. 1 in the journal Cell Host & Microbe.

Their study shows that cocaine use supports the growth of bacteria, which in turn eat a chemical, glycine, that contributes to normal brain function.

As glycine levels decrease, mice show a greater response to the drug with behavioral abnormalities, such as a significant increase in drug-induced locomotion and seeking behavior.

Additionally, by systemically supplementing glycine or using a genetically modified bacterium unable to use glycine, the mice’s response to cocaine drops to normal levels, demonstrating that this amino acid can act as a mediator of addictive-like behavior in animal models.

“I was interested in the gut-brain axis and thought it was very new and exciting,” says first author Santiago Cuesta, a neuroscientist at the University of Wisconsin School of Medicine and Public Health.

Cuesta and colleagues found that when cocaine enters the intestines of mice, it triggers the activation of the QseC protein, which helps the growth of γ-proteobacteria, such as E. coli. These bacteria, fueled by glycine, outcompete the normal gut bacteria already present in our digestive tracts, taking up most of the space and resources.

“Gut bacteria use up all the glycine and levels are reduced systemically and in the brain,” says senior author Vanessa Sperandio, a microbiologist at the University of Wisconsin School of Medicine and Public Health.

This is a drawing of a mouse surrounded by chemical equations
This photo represents the demonstration by Cuesta et al. that cocaine exposure increases norepinephrine in the gut, facilitating colonization by γ-proteobacteria. This shift of gut microbiota toward γ-proteobacteria leads to depletion of host glycine, which in turn facilitates cocaine-induced addictive-like behavior in mice. Credit: Florencia Cerchiara,

“The change in glycine overall appears to affect glutamatergic synapses that make animals more prone to developing addiction.”

“Typically, when it comes to neuroscientific behaviors, people don’t think about controlling the microbiota, and microbiota studies don’t usually measure behaviors, but here we show that they are linked,” says Cuesta. “Our microbiome can actually modulate psychiatric or brain-related behaviors.”

“I think bridging these communities is what will move the field forward, moving beyond correlations to causation for different types of psychiatric disorders,” Sperandio says.

About this news about addiction and microbiome research

Author: Press Office
Source: Cell Press
Contact: Press Office – Cell Press
picture: Image credited to Florencia Cerchiara,

Original Research: Open access.
Gut colonization by proteobacteria alters host metabolism and modulates neurobehavioral responses to cocaine”by Vanessa Sperandio et al. Cellular host and microbe


See also

This shows the brain

Gut colonization by proteobacteria alters host metabolism and modulates neurobehavioral responses to cocaine


  • Cocaine increases the level of norepinephrine in the gut, facilitating the colonization of proteobacteria
  • Proteobacterial colonization depletes glycine in the gut, blood, and CSF of mice
  • Glycine deficiency alters cocaine-induced neuroplasticity and drug responses
  • Systemic or bacterially mediated glycine supplementation restores cocaine responding


Gut microbiota membership is associated with various neuropsychological outcomes, including substance use disorders (SUDs). Here we use mice colonized with s Citrobacter rodentium or commensal of human γ-Proteobacteria Escherichia coli HS as a model for examining mechanistic interactions between gut microbes and the host response to cocaine.

We found that cocaine exposure increases intestinal norepinephrine levels that are heard through the bacterial adrenergic receptor QseC to promote intestinal colonization by γ-proteobacteria.

Colonized mice show enhanced cocaine-induced host behavior. The neuroactive metabolite glycine, a bacterial source of nitrogen, is depleted in the gut and cerebrospinal fluid of colonized mice.

Systemic glycine repletion was reversed, and γ-proteobacteria mutated for glycine uptake did not alter the host’s response to cocaine. Glycine levels modulated by γ-Proteobacteria are associated with cocaine-induced transcriptional plasticity in the nucleus accumbens via glutamatergic transmission.

This mechanism could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.

#gut #bacteria #influence #effects #cocaine #mice

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