Conjugate vaccine produces long-lasting attenuation of fentanyl vs. food choice and blocks expression of opioid withdrawal-induced increases in fentanyl choice in rats.

The current opioid crisis remains a significant public health issue and there is a critical need for biomedical research to develop effective and easily deployable candidate treatments. One emerging treatment strategy for opioid use disorder includes immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness of a fentanyl-tetanus toxoid conjugate vaccine to alter fentanyl self-administration using a fentanyl-vs.-food choice procedure in male and female rats under three experimental conditions. For comparison, continuous 7-day naltrexone (0.01-0.1 mg/kg/h) and 7-day clonidine (3.2-10 mug/kg/h) treatment effects were also determined on fentanyl-vs.-food choice. Male and female rats responded for concurrently available 18% diluted Ensure R (liquid food) and fentanyl (0-10 mug/kg/infusion) infusions during daily sessions. Under baseline and saline treatment conditions, fentanyl maintained a dose-dependent increase in fentanyl-vs.-food choice. First, fentanyl vaccine administration significantly blunted fentanyl reinforcement and increased food reinforcement for 15 weeks in non-opioid dependent rats. Second, surmountability experiments by increasing the unit fentanyl dose available during the self-administration session 10-fold empirically determined that the fentanyl vaccine produced an approximate 22-fold potency shift in fentanyl-vs.-food choice that was as effective as the clinically approved treatment naltrexone. Clonidine treatment significantly increased fentanyl-vs.-food choice. Lastly, fentanyl vaccine administration prevented the expression of withdrawal-associated increases in fentanyl-vs.-food choice following introduction of extended 12 h fentanyl access sessions. Overall, these results support the potential and further consideration of immunopharmacotherapies as candidate treatments to address the current opioid crisis.

52 citations (Crossref) [2023-10-31] Place: England Townsend, E Andrew. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. Blake, Steven. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. Faunce, Kaycee E. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. Hwang, Candy S. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. Hwang, Candy S. Department of Chemistry, Southern Connecticut State University, 501 Crescent St, New Haven, CT, 06515, USA. Natori, Yoshihiro. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. Natori, Yoshihiro. Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Komatsushima 4-4-1, Aoba-ku, Sendai, 981-8558, Japan. Zhou, Bin. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. Bremer, Paul T. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. Janda, Kim D. Departments of Chemistry and Immunology and Microbial Science, Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. kdjanda@scripps.edu. Banks, Matthew L. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA. mbanks7@vcu.edu. Comment in (CIN)