IL-4 mediated by HSV vector suppresses morphine withdrawal response and decreases TNFα, NR2B, and pC/EBPβ in the periaqueductal gray in rats

Yi, Hyun; Iida, Takafumi; Liu, S.; Ikegami, Daigo; Liu, Q.; Iida, Asako; Lubarsky, David A.; Hao, Shuanglin

doi:10.1038/gt.2017.11

Cited by 9 publications

(3 citation statements)

References 72 publications

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“…Although the current study focused solely on weight loss, as it is a prominent symptom of rodent opioid withdrawal, it would be interesting to investigate TNF-α’s effect on other withdrawal behaviors such as wet dog shakes, teeth chattering, and diarrhea. It is possible that these behaviors may also be mediated by TNF-α signaling, as it has been previously shown that downregulating TNF-α signaling in the periaqueductal gray (PAG) of mice decreased the physical symptoms of morphine withdrawal [ 63 ]. In particular, studies have shown that heroin administration can directly stimulate glial toll-like receptor 4 (TLR4) that results in the overexpression of TNF-α and injection of TNF-α into the PAG produces withdrawal symptoms [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss

Parekh

Paniccia²,

Adams³

et al. 2021

Mol Neurobiol

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There is significant comorbidity of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms underlying the relationship between chronic opioid use and withdrawal and development of PTSD are poorly understood. Our previous work identified that chronic escalating heroin administration and withdrawal can produce enhanced fear learning, an animal model of hyperarousal, and is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β). However, other cytokines, such as TNF-α, work synergistically with IL-1β and may have a role in the development of enhanced fear learning. Based on both translational rodent and clinical studies, TNF-α has been implicated in hyperarousal states of PTSD, and has an established role in hippocampal-dependent learning and memory. The first set of experiments tested the hypothesis that chronic heroin administration followed by withdrawal is capable of inducing alterations in DH TNF-α expression. The second set of experiments examined whether DH TNF-α expression is functionally relevant to the development of enhanced fear learning. We identified an increase of TNF-α immunoreactivity and positive cells at 0, 24, and 48 h into withdrawal in the dentate gyrus DH subregion. Interestingly, intra-DH infusions of etanercept (TNF-α inhibitor) 0, 24, and 48 h into heroin withdrawal prevented the development of enhanced fear learning and mitigated withdrawal-induced weight loss. Overall, these findings provide insight into the role of TNF-α in opioid withdrawal and the development of anxiety disorders such as PTSD.

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Section: Discussionmentioning

confidence: 99%

Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss

Parekh

Paniccia²,

Adams³

et al. 2021

Mol Neurobiol

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“…Similarly, opioid withdrawal is mediated by the activation of proinflammatory systems in the PAG. Induction of the interleukin-4 gene (Il4) with a recombinant vector blunted the morphine withdrawal syndrome in mice (59). Microinjection of a herpes simplex virus vector in the PAG to decrease tumor necrosis factor a before the start of morphine treatment significantly reduced naloxoneprecipitated withdrawal in mice (60).…”

Section: Between-system Neuroadaptationsmentioning

confidence: 99%

Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement

Koob

2020

Biological Psychiatry

333

252

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“…We recorded the body weight of each rat before the injection of naloxone and then again at 60 min after naloxone. The scored signs defined in our previous work 24 , were based on our previous experience as modified from those described by Punch et al 13 . A global withdrawal score was calculated for each rat by assigning a combination of the various physical signs of withdrawal 25 .…”

Section: Animal and Evaluation Of Chronic Morphine Physical Dependencementioning

confidence: 99%

Sirt3 mediated by lentiviral vector in the periaqueductal gray suppresses morphine withdrawal in rats: A preliminary study

et al. 2019

Preprint

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Opioid use disorder (OUD) is a significant clinical and social problem, inducing dependence/addiction and over-dose death. Opioid dependence/withdrawal contributes to the addiction vulnerability. Limited understanding of the exact mechanisms of morphine withdrawal leads to failure to adequately manage opioid withdrawal symptoms. Determining new molecular mechanisms of morphine withdrawal (MW) may allow development of novel therapeutic strategies for treating this disorder. Chronic morphine with naloxone precipitation induces MW behavioral response. Sirt3 (one member of sirtuins family) as a mitochondrial fidelity, plays an important role in mitochondrial homeostasis through the direct regulation of mitochondrial energy metabolism, ATP synthesis, detoxification of mitochondrial ROS, etc. In the pilot study, we found that (1) cultured neurons infected with lentiviral vector expressing Sirt3 induced over-expression of Sirt3, (2) microinjection of LV-Sirt3 into the vlPAG increased Sirt3 protein expression in rats, (3) MW lowered the expression of Sirt3 in the vlPAG, and (4) microinjection of LV-Sirt3 into the vlPAG decreased the MW behavioral response. Current preliminary study demonstrates that complement of Sirt3 in the PAG suppressed MW, providing a novel therapeutic approach to morphine physical withdrawal symptoms. The exact up-and/or down-stream factors of Sirt3 in the model are under the investigation.

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IL-4 mediated by HSV vector suppresses morphine withdrawal response and decreases TNFα, NR2B, and pC/EBPβ in the periaqueductal gray in rats

Cited by 9 publications

References 72 publications

Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss

Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss

Neurobiology of Opioid Addiction: Opponent Process, Hyperkatifeia, and Negative Reinforcement

Sirt3 mediated by lentiviral vector in the periaqueductal gray suppresses morphine withdrawal in rats: A preliminary study

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