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Cocaine alters the balance of microbes in the mice’s guts, part of a cycle of waxing and waning neurochemicals that can enhance the drug’s effects on the brain. But the same chemicals can also be harnessed to prevent addiction, according to new research from the University of Wisconsin-Madison.

Cocaine increases levels of a hormone called norepinephrine in users’ intestines, causing an explosion of growth of proteobacteria, a family of microbes that includes the common and sometimes harmful bacterium E. coli.

Vanessa Sperandio

“All this colonizing E. coli needs nitrogen to grow, and its favorite food is glycine, an amino acid that works in the brain as a neurotransmitter,” says Vanessa Sperandio, professor and chair of Medical Microbiology and Immunology at UW-Madison’s School of Medicine. of Medicine and Public Health and co-author of a study recently published in the journal Cell Host & Microbe. “Therefore, an overgrowth of E. coli causes glycine levels to drop throughout the body, including in a pathway in the brain where glycine manages the response to cocaine.”

The researchers administered cocaine to a group of mice infected with proteobacteria, either a strain of E. coli isolated from humans or a similar type of bacteria that infects rodents, and found that mice carrying the proteobacteria experienced more cocaine-induced locomotion and cocaine-seeking. behavior than mice without proteobacteria in their intestines.

“With their glycine depleted, they were more sensitive to cocaine and more prone to addiction than mice with normal gut microbiota,” says Sperandio.

The researchers then introduced another group of mice with a strain of E. coli without genes that allow the bacteria to eat glycine. When these mice encountered cocaine, they were less affected by the drug.

“E. coli still responded to norepinephrine and colonized the mouse gut, but had to find a different food source than glycine,” says Sperandio. “This shows us that it’s glycine depletion that affects the brain. Avoid glycine depletion and the mice don’t respond to cocaine by trying to get more and more of it.”

It’s an important step in understanding the biochemistry of cocaine addiction, the researchers say, and may present a way to prevent humans from getting hooked. Altering the types and proportions of microbes in the human gut is incredibly complicated and would almost certainly have unintended effects beyond any addiction-related benefits.

“But luckily, we already know that glycine and sarcosine, an amino acid the body uses to make glycine, are nontoxic and easy to take,” says Sperandio, whose work is supported by the National Institutes of Health.

Sarcosine is a relatively common nutritional supplement popular among athletes and already available in stores.

“There’s a lot of work to be done to translate this to humans,” says Sperandio, whose research is supported by the National Institutes of Health. “But now that we’ve isolated this addictive mechanism in mice, we can explore methods to disrupt it, possibly in ways as simple as supplementing glycine and sarcosine in the body.”

UW-Madison staff scientist Santiago Cuesta led the study, working with collaborators at the University of Texas Southwestern Medical Center, the Rosario Institute of Molecular and Cellular Biology in Argentina, and Concordia University and the University of Quebec in Montreal.

This research was supported by grants from the National Institutes of Health (AI053067, AI154597, and AI155398).

Source: The brain-gut connection may reveal a way to prevent cocaine addiction