Speaker: Michelle Ren
Location: College of Health Sciences, Room 2110
“The Bidirectional Relationship Between Gut Microbiota and Intravenous Fentanyl Self-Administration”
Presentation Synopsis: The United States is currently experiencing its worst drug crisis, which is largely driven by opioid addiction and primarily due to fentanyl. It is therefore necessary to investigate the mechanisms mediating fentanyl’s rewarding and reinforcing properties to contribute to the development of successful treatment strategies. Gut bacteria communicate with the brain, and vice versa, via the gut-brain axis to regulate brain function, mood, and behavior. Addiction is a chronic brain disorder that alters circuitry involved in reward, stress, learning, and motivation, all of which have a bidirectional influence between their associated behaviors and gut bacteria. Given the associations between opioid use, gastrointestinal distress, and microbial dysbiosis in humans and rodents, I tested the hypothesis that interactions between gut bacteria and the brain mediate the reinforcing and motivational properties of fentanyl. In the following studies, I implanted rats with intravenous catheters in preparation for fentanyl intravenous self-administration (IVSA) on an escalating schedule of reinforcement and analyzed gut microbiota by sequencing bacterial DNA from rat fecal samples. I demonstrate that 1) fentanyl IVSA changes the alpha diversity of gut bacteria in a sex-dependent manner, 2) depletion of gut bacteria enhances fentanyl IVSA, and 3) restoration of bacterial metabolites reverses the enhancement of fentanyl IVSA. My findings highlight an important relationship between the knockdown and rescue of gut bacterial metabolites and fentanyl self-administration in adult rats, which provides support for a relationship between gut microbiota and opioid use. Further work in this area may lead to effective, targeted treatment interventions in opioid-related disorders.