Regional Fos expression induced by morphine withdrawal in the 7-day-old rat

McPhie, Anika A.; Barr, Gordon A.

doi:10.1002/dev.20392

Cited by 11 publications

(13 citation statements)

References 67 publications

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“…To probe the mechanism of how con-T[M8Q] inhibits morphine dependence with such a high potency, the effects of con-T[M8Q] on the expression of NMDAR-related signal proteins, such as GluN2B, p-GluN2B, CaMKII-α, CaMKII-β, CaMKIV, nNOS, PKC-γ, and c-fos, were investigated. Before the administration of con-T[M8Q], the expression of GluN2B, p-GluN2B,c-fos and CaMKII-β proteins increases significantly after morphine administration, consistent with the literature [ 36 , 37 , 38 , 39 , 40 ]. After the administration of con-T[M8Q], the increased mRNA or protein levels of above proteins decrease significantly in the hippocampus ( Figure 5 and Figure 6 ).…”

Section: Discussionsupporting

confidence: 87%

A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects

Liu¹,

Zheng²,

Yu³

et al. 2021

Marine Drugs

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N-methyl-D-aspartate receptor (NMDAR) antagonists have been found to be effective to inhibit morphine dependence. However, the discovery of the selective antagonist for NMDAR GluN2B with low side-effects still remains challenging. In the present study, we report a selective NMDAR GluN2B antagonist con-T[M8Q](a conantokin-T variant) that potently inhibits the naloxone-induced jumping and conditioned place preference of morphine-dependent mice at nmol/kg level, 100-fold higher than ifenprodil, a classical NMDAR NR2B antagonist. Con-T[M8Q] displays no significant impacts on coordinated locomotion function, spontaneous locomotor activity, and spatial memory mice motor function at the dose used. Further molecular mechanism experiments demonstrate that con-T[M8Q] effectively inhibited the transcription and expression levels of signaling molecules related to NMDAR NR2B subunit in hippocampus, including NR2B, p-NR2B, CaMKII-α, CaMKII-β, CaMKIV, pERK, and c-fos. The high efficacy and low side effects of con-T[M8Q] make it a good lead compound for the treatment of opiate dependence and for the reduction of morphine usage.

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Section: Discussionsupporting

confidence: 87%

A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects

Liu¹,

Zheng²,

Yu³

et al. 2021

Marine Drugs

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show abstract

“…Currently, there are no clinical, physiological, or biochemical markers to identify patients developing opioid tolerance. In animal models, opioid tolerance is assessed by a need for increased doses and the signs of opioid withdrawal precipitated by giving opioid antagonists (36, 37). This approach is not clinically feasible; therefore, future research must focus on a search for reliable biomarkers that can allow us to investigate the real-time relationships between opioid analgesia, hyperalgesia, tolerance, and withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Opioid Analgesia in Mechanically Ventilated Children

Anand

Clark

Willson

et al. 2013

Pediatric Critical Care Medicine

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Objective To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the Pediatric Intensive Care Unit (PICU). Design Prospective, observational study with 100% accrual of eligible patients. Setting Seven PICUs from tertiary-care children’s hospitals in the Collaborative Pediatric Critical Care Research Network. Patients 419 children treated with morphine or fentanyl infusions. Interventions None Measurements and Main Results Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95%CI: 12–19%) and 20% patients (95%CI: 16–24%) respectively. Among patients receiving opioids for longer than 3 days (n=225), this occurred in 28% (95%CI 22–33%) and 35% (95%CI 29–41%) by 7 or 14 days respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (OR 7.9, 95%CI 4.3–14.3; p<0.001) or co-therapy with midazolam (OR 5.6, 95%CI 2.4–12.9; p<0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (OR 0.48, 95%CI 0.25–0.92; p=0.03), for patients receiving higher initial doses (OR 0.96, 95%CI 0.95–0.98; p<0.001), or if patients had prior PICU admissions (OR 0.37, 95%CI 0.15–0.89, p=0.03). Conclusions Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

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“…TNFa in morphine withdrawal S Hao et al of neuronal activity (Castilho et al, 2008;Chieng et al, 1995;McPhie and Barr, 2009). In this study, the expression of Fos was evaluated by counting the number of Fos immunopositive cells in the PAG.…”

Section: Tnfsr Released By the Hsv Vector In The Pag Prevents Astrocymentioning

confidence: 99%

The Role of TNFα in the Periaqueductal Gray During Naloxone-Precipitated Morphine Withdrawal in Rats

Hao

Zheng

et al. 2010

Neuropsychopharmacol

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Tolerance and dependence are common complications of long-term treatment of pain with opioids, which substantially limit the long-term use of these drugs. The mechanisms underlying these phenomena are poorly understood. Studies have implicated the midbrain periaqueductal gray (PAG) in the pathogenesis of morphine withdrawal, and recent evidence suggests that proinflammatory cytokines in the PAG may play an important role in morphine withdrawal. Here we report that chronic morphine withdrawal-induced upregulation of glial fibrillary acidic protein (GFAP), tumor necrosis factor alpha (TNFα) and phosphorylation of ERK1/2 (pERK1/2) in the caudal ventrolateral PAG (vlPAG). Microinjection of recombinant TNFα into the vlPAG followed by intraperitoneal naloxone resulted in morphine withdrawal-like behavioral signs, and upregulation of pERK1/2, expression of Fos, and phosphorylation of cAMP response element binding (pCREB) protein. We used a herpes simplex virus (HSV)-based vector expressing p55 soluble TNF receptor (sTNFR) microinjected into the PAG to examine the role of the proinflammatory cytokine TNFα in the PAG in the naloxone-precipitated withdrawal response. Microinjection of HSV vector expressing sTNFR into the PAG before the start of morphine treatment significantly reduced the naloxone-precipitated withdrawal behavioral response and downregulated the expression of GFAP and TNFα in astrocytes of the PAG. TNFR type I colocalized with neuronal pERK1/2. Microinjection of HSV vector expressing sTNFR into the PAG also significantly reduced the phosphorylation of both ERK1/2 and CREB, and reduced Fos immunoreactivity in neurons of the PAG following naloxone-precipitated withdrawal. These results support the concept that proinflammatory cytokines expressed in astrocytes in the PAG may play an important role in the pathogenesis of morphine withdrawal response.

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Regional Fos expression induced by morphine withdrawal in the 7-day-old rat

Cited by 11 publications

References 67 publications

A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects

A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects

Opioid Analgesia in Mechanically Ventilated Children

The Role of TNFα in the Periaqueductal Gray During Naloxone-Precipitated Morphine Withdrawal in Rats

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