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
- 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
- In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.
- Authors: Singh P, Sharma B, Gupta S, Sharma BM
- Issue date: 2015 Jan
- Effects of fentanyl dose and exposure duration on the affective and somatic signs of fentanyl withdrawal in rats.
- Authors: Liu J, Pan H, Gold MS, Derendorf H, Bruijnzeel AW
- Issue date: 2008 Oct
- Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents.
- Authors: Doyle TM, Hutchinson MR, Braden K, Janes K, Staikopoulos V, Chen Z, Neumann WL, Spiegel S, Salvemini D
- Issue date: 2020 Oct 22
- The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.
- Authors: Sirohi S, Dighe SV, Madia PA, Yoburn BC
- Issue date: 2009 Aug