Gut microbes may influence how rat brains respond to opioids

Written by Sharon Salt, Senior Editor

A recent study has indicated that gut microbes could influence the pattern of activation in a rat’s brain during opioid addiction and withdrawal. The results, which have been published in eNeuro, also suggest that taking antibiotics alongside opioids may increase the risk of opioid abuse.

Opioids and antibiotics are commonly prescribed together following surgery in order to treat pain while fighting off infection. However, this common drug combination can also kill gut microbes. Given the prevalence of their combination, the researchers of the present study wanted to explore the relationship of these two types of drugs.

In their study, the investigators administered antibiotics to rats for 2 weeks to deplete their gut microbiome and then gave them the opioid oxycodone.

In comparison with the rats that only received oxycodone, the microbiome-depleted rats demonstrated profound changes in how their brains responded to opioids.

According to the investigators, the typical pattern of neuron recruitment to different parts of the brain during intoxication and withdrawal was disrupted in rats that had been treated with antibiotics (i.e., rats lacking most of their gut microbes).

During intoxication, rats with depleted gut microbes were reported to have more activated neurons in the regions of the brain that regulate stress and pain (periaqueductal gray, locus coeruleus) and regions involved in opioid intoxication and withdrawal (central amygdala, basolateral amygdala). During withdrawal, microbe-depleted rats had fewer activated neurons in the central amygdala, as compared with rats that had normal gut microbiomes.

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“It was many months of counting black dots. But in the end it became clear that, at least in rats, gut microbes alter the way the brain responds to drugs,” commented study author, Sierra Simpson (University of California San Diego, CA, USA).

Simpson explained that this shift could affect behavior, as a decrease in neurons recruited in the central amygdala could result in fewer withdrawal symptoms, which in turn could lead to a higher risk of drug abuse.

“Not only does this study suggest gut microbes may play a role in drug addiction, if we find similar effects in humans, it may change the way we think about co-prescribing antibiotics and pain killers, for example when a person undergoes surgery. The way a person’s gut microbes are affected could make them more or less sensitive to the opioids. The key now will be looking for biomarkers so we can predict how a person might respond before we treat them,” concluded co-author, Olivier George (University of California San Diego).

In future, the team plan to search for microbial or chemical signatures in rats that could indicate which are more susceptible to addiction, with and without gut microbes. Moreover, the researchers are mining human microbiome data – including users of opioids and antibiotics – to see if they follow trends similar to those they observed in rats.

Sources: Simpson S et al. Antibiotic depletion of the microbiome alters the recruitment of neuronal ensembles of oxycodone intoxication and withdrawal. eNeuro doi:10.1523/ENEURO.0312-19.2020 (2020);;–gmi042120.php