Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

Uddin, Olivia; Jenne, Carleigh; Fox, Megan E.; Arakawa, Keiko; Keller, Asaf; Cramer, Nathan

doi:10.1016/j.pbb.2020.173077

Cited by 29 publications

(20 citation statements)

References 70 publications

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“…In the present study, fentanyl and heroin were used as positive controls and dose comparisons because they have been shown to serve as a reinforcing stimulus to induce CPP, self-administration and opioid withdrawal significantly in rodents. 3,4,24,25 The present study reports an assessment of rewarding, reinforcing and physical dependence of carfentanil for the first time. The CPP and drug self-administration tests have been widely used to assess the psychological dependence, which revealed the rewarding and reinforcing effects of drugs.…”

Section: Discussionmentioning

confidence: 96%

Assessment of abuse potential of carfentanil

Wei

Lai

et al. 2023

Addiction Biology

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Carfentanil, as a fentanyl analogue, is a potent synthetic opioid. It has been controlled in many countries, and its emergence has been highlighted by many recent reports.However, although discriminative stimulus effects of carfentanil in rats had been reported, its abuse potential has not been fully evaluated. In this study, we evaluated the abuse potential of carfentanil via the tests of conditioned place preference (CPP), drug self-administration and naloxone-precipitated opioid withdrawal assay, com-

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Section: Discussionmentioning

confidence: 96%

Assessment of abuse potential of carfentanil

Wei

Lai

et al. 2023

Addiction Biology

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“…A blinded experimenter scored withdrawal signs for 10 min and determined bodyweight loss after 1hr. Points were assigned as previously (Uddin et al, 2021). (Graded signs: wet dog shakes: 1-2, 2 points; 2+, 4 points; Escape jumps: 2-4, 1 point, 5-9, 2 points, 10+, 3 points; paw tremors: 1-2, 2 points, 3+, 4 points; bodyweight loss in 60 min, 1 point per each 1%; Checked Signs: diarrhea, swallowing movements, teeth chattering, all 2 points each; genital grooming, abnormal posture, 3 points each).…”

Section: Star Methodsmentioning

confidence: 99%

Negative emotional behavior during fentanyl abstinence is mediated by adaptations in nucleus accumbens neuron subtypes

Fox

Wulff

Franco

et al. 2022

Preprint

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SummaryOpioid discontinuation generates a withdrawal syndrome marked by a negative emotional state. Increased anxiety and dysphoria during opioid discontinuation are a significant barrier to achieving long-term abstinence in opioid-dependent individuals. Adaptations in brain-reward circuitry are implicated in the opioid abstinence syndrome, but current knowledge is limited to changes following natural and semi-synthetic opioids. Here we report abstinence from the synthetic opioid fentanyl engenders structural, functional, and molecular plasticity in nucleus accumbens neuron subtypes (MSNs) that mediate negative emotional behaviors. We show fentanyl abstinence causes dendritic atrophy and increased excitatory drive exclusive to D1-receptor containing MSNs. Using subtype specific RNAseq and Weighted Gene Co-Expression Network Analysis, we identified molecular signatures of fentanyl abstinence in MSN subtypes. We found a network of co-expressed genes downregulated selectively in D1-MSNs, and transcriptionally co-regulated by E2F1. We show targeting abstinence-induced molecular changes protects D1-MSNs from maladaptive plasticity and alleviates negative emotional behaviors after fentanyl abstinence.

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“…The results carried out in the LC from mice were similar but not identical in that the degree of tolerance induced by morphine in the mouse LC is qualitatively less than that measured in rat ( Quillinan et al, 2011 ). There is also a difference in signs of acute withdrawal between mice and rat indicating a marked species difference in the adaptive processes following chronic treatment with opioids ( Uddin et al, 2021 ).…”

Section: Areas Where Neurons Have Been Examined Following Chronic Mor...mentioning

confidence: 99%

Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System

Adhikary

Williams

2022

Front. Syst. Neurosci.

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Opioids are powerful analgesics that elicit acute antinociceptive effects through their action the mu opioid receptor (MOR). However opioids are ineffective for chronic pain management, in part because continuous activation of MORs induces adaptive changes at the receptor level and downstream signaling molecules. These adaptations include a decrease in receptor-effector coupling and changes to second messenger systems that can counteract the persistent activation of MORs by opioid agonists. Homeostatic regulation of MORs and downstream signaling cascades are viewed as precursors to developing tolerance. However, despite numerous studies identifying crucial mechanisms that contribute to opioid tolerance, no single regulatory mechanism that governs tolerance in at the cellular and systems level has been identified. Opioid tolerance is a multifaceted process that involves both individual neurons that contain MORs and neuronal circuits that undergo adaptations following continuous MOR activation. The most proximal event is the agonist/receptor interaction leading to acute cellular actions. This review discusses our understanding of mechanisms that mediate cellular tolerance after chronic opioid treatment that, in part, is mediated by agonist/receptor interaction acutely.

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Divergent profiles of fentanyl withdrawal and associated pain in mice and rats

Cited by 29 publications

References 70 publications

Assessment of abuse potential of carfentanil

Assessment of abuse potential of carfentanil

Negative emotional behavior during fentanyl abstinence is mediated by adaptations in nucleus accumbens neuron subtypes

Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System

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