Divergent profiles of fentanyl withdrawal and associated pain in mice and rats
JournalPharmacology, Biochemistry, and Behavior
MetadataShow full item record
AbstractOpioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species' strengths as model systems and can inform experimental design in studies of opioid withdrawal.
Rights/TermsCopyright © 2020 Elsevier Inc. All rights reserved.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/14303
- Methocinnamox Produces Long-Lasting Antagonism of the Behavioral Effects of <i>µ</i>-Opioid Receptor Agonists but Not Prolonged Precipitated Withdrawal in Rats.
- Authors: Gerak LR, Minervini V, Latham E, Ghodrati S, Lillis KV, Wooden J, Disney A, Husbands SM, France CP
- Issue date: 2019 Nov
- The effects of buprenorphine on fentanyl withdrawal in rats.
- Authors: Bruijnzeel AW, Marcinkiewcz C, Isaac S, Booth MM, Dennis DM, Gold MS
- Issue date: 2007 May
- Involvement of supraspinal and peripheral naloxonazine-insensitive opioid receptor sites in the expression of μ-opioid receptor agonist-induced physical dependence.
- Authors: Mori T, Komiya S, Uzawa N, Inoue K, Itoh T, Aoki S, Shibasaki M, Suzuki T
- Issue date: 2013 Sep 5
- Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe for drug-related motivational states.
- Authors: Fendt M, Mucha RF
- Issue date: 2001 May
- Mechanical allodynia and thermal hyperalgesia upon acute opioid withdrawal in the neonatal rat.
- Authors: Sweitzer SM, Allen CP, Zissen MH, Kendig JJ
- Issue date: 2004 Jul