How Gut Bacteria Influence the Effects of Cocaine in Mice

Summary: Cocaine use promotes the growth of γ-proteobacteria, a common gut bacterium that consumes glycine. As glycine levels are depleted, mouse models show a higher response to cocaine with abnormal behaviors including increased drug-induced locomotion and drug-seeking behaviors.

Source: Cell press

Common gut bacteria may potentiate the effects of cocaine in mice, researchers report Nov. 1 in the journal Cell host and microbe.

Their study demonstrates how cocaine use promotes the growth of bacteria, which in turn devours a chemical, glycine, which contributes to normal brain function.

As glycine levels are depleted, mice show a higher response to the drug with behavioral abnormalities, such as a significant increase in drug-induced locomotion and seeking behaviors.

Moreover, by supplementing glycine systemically or by using a genetically engineered bacterium that cannot utilize glycine, the mice’s response to cocaine fell back to normal levels, demonstrating that this amino acid can act as a behavioral mediator of addiction in animal models.

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

Cuesta and his colleagues found that when cocaine enters the gut 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 that already exist in our digestive tracts, taking up most of the space and resources.

“Gut bacteria consume all of the glycine, and levels decline systemically and in the brain,” says lead 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 of Cuesta et al. that exposure to cocaine increases norepinephrine in the gut facilitating colonization by γ-proteobacteria. This shift of gut microbiota to γ-proteobacteria leads to host glycine depletion, which, in turn, facilitates cocaine-induced addiction-like behaviors in mice. Credit: Florencia Cerchiara,

“It appears that global glycine modification impacts glutamatergic synapses that make animals more prone to addiction.”

“Usually for behaviors in neuroscience, people don’t think about controlling the microbiota, and microbiota studies don’t usually measure behaviors, but here we show they’re connected,” Cuesta says. “Our microbiome can actually modulate psychiatric or brain-related behaviors.”

“I think bringing these communities together is what’s going to move the field forward, moving beyond correlations to the causes of different types of psychiatric disorders,” Sperandio says.

About this addiction and microbiome research news

Author: Press office
Source: Cell press
Contact: Press office – Cell press
Image: Image is credited to Florencia Cerchiara,

Original research: Free access.
“Intestinal colonization by proteobacteria alters host metabolism and modulates neurobehavioral responses to cocaine” by Vanessa Sperandio et al. Cell host and microbe


See also

It shows a brain

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

Strong points

  • Cocaine increases intestinal norepinephrine levels facilitating colonization of proteobacteria
  • Proteobacteria colonization depletes glycine in intestine, blood and CSF in mice
  • Glycine depletion alters cocaine-induced neuroplasticity and drug responses
  • Systemic or bacterial-mediated glycine replenishment restores responses to cocaine


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

We find that cocaine exposure increases intestinal norepinephrine levels which are sensed by the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-proteobacteria.

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

Systemic glycine repletion was reversed, and glycine-uptake mutated γ-proteobacteria did not alter the host response to cocaine. Glycine levels modulated by γ-proteobacteria are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission.

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

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