Project 466887

Canada is currently facing an opioid crisis, with approximately 20 Canadians dying daily due to opioid overdose. Relapse following treatment for opioid addiction is common, and novel strategies are needed to reduce the likelihood of relapse. This project aims to explore the gut microbiome as a possible target for treatment during opioid withdrawal. Not only has the acute phase of opioid withdrawal been shown to alter the gut microbiota in mice, but fecal transfers from opioid-withdrawn to drug-naive mice are able to induce symptoms of opioid withdrawal. However, it has yet to be determined if the relationship between the microbiome and opioid withdrawal symptoms is sustained during longer periods of abstinence. This project aims to characterize the protracted opioid withdrawal phenotype in mice, and to determine if alterations in the microbiome are necessary for this phenotype to occur. This will include characterization of the symptoms of protracted withdrawal in mice, including mechanical and thermal hyperalgesia (assessed via von Frey filaments and tail-withdrawal assays, respectively), anxiety (using an elevated plus maze and open field test), and neuroinflammation in post-mortem tissue. Fecal samples from drug-naïve animals, as well as animals in various stages of opioid withdrawal, will be used to assess changes in the gut microbiota, and fecal matter from mice in various stages of opioid withdrawal will be used in fecal transfers to recolonize the gastrointestinal tract of germ-free mice. If the relationship between the gut microbiome and symptoms of withdrawal persists, interventions that aim to restore the composition of the gut microbiome could prove to be an attractive target in alleviating the withdrawal symptoms associated with chronic opioid use.