Lindsey R Hammerslag1, Rebecca S Hofford1, Qiwen Kang2, Richard J Kryscio2, Joshua S Beckmann1, Michael T Bardo3. 1. Department of Psychology, University of Kentucky, 741 S. Limestone St., Lexington, KY, 40536, USA. 2. Department of Statistics, University of Kentucky, 800 S. Limestone St., Lexington, KY, 40536, USA. 3. Department of Psychology, University of Kentucky, 741 S. Limestone St., Lexington, KY, 40536, USA. Electronic address: mbardo@uky.edu.
Abstract
BACKGROUND: Individuals with opioid use disorder (OUD) exhibit high levels of economic demand for opioids, with high levels of consumption and relative insensitivity to changes in price. Because the medications used to treat OUD in medication-assisted therapy (MAT) act as antagonists or agonists at μ opioid receptors, they may alter the relationship between price and opioid intake. METHODS: This study examined demand for a commonly abused synthetic prescription opioid, fentanyl, in male rats following s.c. pre-treatment with naltrexone (0.1-1.0 mg/kg), morphine (0.3-3.0 mg/kg) or buprenorphine (0.3-3.0 mg/kg). We normalized demand curves to intake at the lowest price and estimated effects on elasticity (sensitivity to changes in price). Rats were first trained to earn fentanyl (5 μg/kg/infusion) on a fixed ratio schedule, then they underwent daily training under a threshold procedure designed to produce within-session demand curve estimates. Rats received 14 threshold sessions before undergoing a series of tests encompassing each drug, at each dose. RESULTS: Elasticity was increased by pretreatment with naltrexone, morphine or buprenorphine. Morphine also decreased initial intake, when the price for fentanyl was lowest. In contrast, initial intake was increased by naltrexone (according to an inverted-U shaped curve). The effects of naltrexone did not persist after the test session, but morphine and buprenorphine continued affecting demand elasticity 24 h or 48 h after the test, respectively. CONCLUSIONS: These results indicate that fentanyl demand is sensitive to blockade or activation of opioid receptors by the drug classes used for MAT in humans.
BACKGROUND: Individuals with opioid use disorder (OUD) exhibit high levels of economic demand for opioids, with high levels of consumption and relative insensitivity to changes in price. Because the medications used to treat OUD in medication-assisted therapy (MAT) act as antagonists or agonists at μ opioid receptors, they may alter the relationship between price and opioid intake. METHODS: This study examined demand for a commonly abused synthetic prescription opioid, fentanyl, in male rats following s.c. pre-treatment with naltrexone (0.1-1.0 mg/kg), morphine (0.3-3.0 mg/kg) or buprenorphine (0.3-3.0 mg/kg). We normalized demand curves to intake at the lowest price and estimated effects on elasticity (sensitivity to changes in price). Rats were first trained to earn fentanyl (5 μg/kg/infusion) on a fixed ratio schedule, then they underwent daily training under a threshold procedure designed to produce within-session demand curve estimates. Rats received 14 threshold sessions before undergoing a series of tests encompassing each drug, at each dose. RESULTS: Elasticity was increased by pretreatment with naltrexone, morphine or buprenorphine. Morphine also decreased initial intake, when the price for fentanyl was lowest. In contrast, initial intake was increased by naltrexone (according to an inverted-U shaped curve). The effects of naltrexone did not persist after the test session, but morphine and buprenorphine continued affecting demand elasticity 24 h or 48 h after the test, respectively. CONCLUSIONS: These results indicate that fentanyl demand is sensitive to blockade or activation of opioid receptors by the drug classes used for MAT in humans.
Authors: Paul Glue; Gavin Cape; Donna Tunnicliff; Michelle Lockhart; Fred Lam; Andrew Gray; Noelyn Hung; C Tak Hung; Sarah Harland; Jane Devane; John Howes; Holger Weis; Lawrence Friedhoff Journal: J Clin Pharmacol Date: 2016-02-29 Impact factor: 3.126
Authors: Matthew J Horchar; Joy L Kappesser; Maria R Broderick; Makayla R Wright; Justin R Yates Journal: Drug Alcohol Depend Date: 2022-02-12 Impact factor: 4.492
Authors: E Andrew Townsend; Bruce E Blough; David H Epstein; S Stevens Negus; Yavin Shaham; Matthew L Banks Journal: Neuropsychopharmacology Date: 2022-07-29 Impact factor: 8.294
Authors: Sam A McConnell; Adam J Brandner; Brandon A Blank; David N Kearns; George F Koob; Leandro F Vendruscolo; Brendan J Tunstall Journal: Neuropharmacology Date: 2020-10-20 Impact factor: 5.250
Authors: E Andrew Townsend; Kathryn L Schwienteck; Hannah L Robinson; Stephen T Lawson; Matthew L Banks Journal: J Neurosci Methods Date: 2021-03-08 Impact factor: 2.390