Repeated Use of Morphine Induces Anxiety by Affecting a Proinflammatory Cytokine Signaling Pathway in the Prefrontal Cortex in Rats

Ahmadi, Shamseddin; Talvar, Shiva Mohammadi; Masoudi, Kayvan; Zobeiri, Mohammad

doi:10.1007/s12035-022-03144-3

Cited by 5 publications

(2 citation statements)

References 82 publications

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“…The activation of the MAPK and NF-κB signaling pathways by morphine has been confirmed by numerous studies (Ji et al, 2020;Ren et al, 2022;Ahmadi et al, 2023;Yang et al, 2023). However, the role of Toll-like receptor 4 (TLR4) in this process remains highly controversial (Eisenstein, 2019;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 97%

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Chen,

Liu,

Huang

2024

Front. Pharmacol.

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BackgroundThe effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action.MethodsBy repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4+ T cells and CD8+ T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered.ResultsRepeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4+ T cells, with little effect on CD8+ T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees.ConclusionRepeated intraperitoneal injection of oxycodone induces immunosuppression in mice.

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Section: Introductionmentioning

confidence: 97%

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Chen,

Liu,

Huang

2024

Front. Pharmacol.

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“…Opioid-induced alterations have mainly been associated with the direct induction of apoptotic pathways in neurons [19,20] as well as with opioid-induced generation of neuroinflammation and oxidative stress in specific brain areas, including the prefrontal cortex, neostriatum, and nucleus accumbens [19,[21][22][23], which are brain areas mainly associated with drug dependence and loss of control over drug intake [24]. In the microglia and astrocytes, opioids, like other addictive drugs, directly activate the foreign molecule sensing toll-like receptor 4 (TLR-4), leading to the activation of the transcription factor NF-κB and production of pro-inflammatory mediators such as TNF-α, IL-1β, and IL-6 [25,26].…”

Section: Introductionmentioning

confidence: 99%

Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

Quintanilla,

Morales,

Santapau

et al. 2023

IJMS

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Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

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Alpha-Pinene Decreases the Elevated Levels of Astrogliosis, Pyroptosis, and Autophagy Markers in the Hippocampus Triggered by Kainate in a Rat Model of Temporal Lobe Epilepsy

Hashemi,

Mardani,

Eghbali Raz

et al. 2024

Mol Neurobiol

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Repeated Use of Morphine Induces Anxiety by Affecting a Proinflammatory Cytokine Signaling Pathway in the Prefrontal Cortex in Rats

Cited by 5 publications

References 82 publications

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice

Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

Alpha-Pinene Decreases the Elevated Levels of Astrogliosis, Pyroptosis, and Autophagy Markers in the Hippocampus Triggered by Kainate in a Rat Model of Temporal Lobe Epilepsy

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