Abstract
Communication between the brain and gut bacteria impacts drug- and addiction-related behaviors. To investigate the role of gut microbiota on fentanyl reinforcement and reward, we depleted gut bacteria in adult Sprague Dawley male and female rats using an oral, nonabsorbable antibiotic cocktail and allowed rats to intravenously self-administer fentanyl on an escalating schedule of reinforcement. We found that antibiotic treatment enhanced fentanyl self-administration in males, but not females, at the lowest schedule of reinforcement (i.e., fixed ratio 1). Both males and females treated with antibiotics self-administered greater amounts of fentanyl at higher schedules of reinforcement. We then replete microbial metabolites via short-chain fatty acid administration to evaluate a potential mechanism in gut-brain communication and found that restoring metabolites decreases fentanyl self-administration back to controls at higher fixed ratio schedules of reinforcement. Our 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 significant relationship between the gut microbiome and opioid use. Further work in this field may lead to effective, targeted treatment interventions in opioid-related disorders.
Funder
the University of California Irvine (UCI) NIDA T32 training
UCI School of Medicine start-up fund
UCI Institute for Clinical and Translational Sciences (ICTS) Pilot Studies Program
Helping End Addiction Long-Term (HEAL) Initiative Opioid-Related Pilot Studies Program
UCI School of Medicine Start Up funds
UCI Microbiome Initiative Pilot Studies Grant
Tobacco-Related Disease Research Program
NIH Grant
UCI Department of Emergency Medicine Pilot Grant
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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