Mice with high FGF21 serum levels had a reduced preference for morphine and an attenuated development of acute antinociceptive tolerance and physical dependence. (1st January 2022)

• Record Type: Journal Article
• Authors: Dorval, Louben; Knapp, Brian I.; Majekodunmi, Olufolake A.; Eliseeva, Sophia; Bidlack, Jean M.
• Is Part Of: Neuropharmacology. Volume 202(2022)
• Publication Date: 2022-01-01
• Subjects: Morphine -- Reward -- Antinociception -- Tolerance/dependence -- FGF21 -- Respiratory depression; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108858
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Because of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55 °C hot plate and the 55 °C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had a decrease in the development of acute analgesic tolerance, and the development of physical dependence, and morphine preference. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain patients to minimize tolerance development. Graphical abstract: Image 1 Highlights: Mice expressing high FGF21 serum levels had a reduced preference for morphine. FGF21-Tg mice had an attenuated physical dependence to morphine. FGF21-Tg mice had a reduced acute, but not chronic, development of morphine tolerance. Morphine-induced antinociception and respiratory depression were not altered in FGF21-Tg mice. The FGF21 receptor may be a target to minimize acute opioid tolerance development, and physical and psychological dependence.