Bupropion attenuates morphine tolerance and dependence: Possible role of glutamate, norepinephrine, inflammation, and oxidative stress

Hamdy, Mostafa M.; Elbadr, Mohamed M.; Barakat, Ahmed

doi:10.1016/j.pharep.2018.04.003

Cited by 15 publications

(16 citation statements)

References 52 publications

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“…34 Cerebral oxidative stress has been well described during acute opioid withdrawal. [14][15][16] Using in vivo MRS, we were able to demonstrate a significant decrease in [GSH] at 120 min after naloxone, compared with pre-withdrawal scans within the salinetreated group, and a significantly lower [GSH] at 120 min after naloxone in OD rats treated with saline vs NAC. Pre-withdrawal GSH concentrations were not significantly different between groups.…”

Section: Discussionmentioning

confidence: 87%

“…In an adult opioid-dependent animal model, other investigators have determined that withdrawal precipitates oxidative stress, and measures of oxidative stress directly relate to withdrawal behaviors, which are responsive to antioxidants. [14][15][16] In addition to oxidative stress, there is a disruption of glutamate homeostasis during opioid withdrawal resulting in an increase in synaptic glutamate (excitatory neurotransmitter) that leads to increased neuronal firing. [17][18][19][20][21] This increase in synaptic glutamate occurs because of decreased tone and function of the extrasynaptic metabotropic glutamate autoreceptors, mGluR2/3, which normally inhibits synaptic glutamate release (this decreased inhibition leads to increased synaptic glutamate) 17,20 and decreased function of glial glutamate transporter-1, which causes reduced glutamate elimination from extracellular space resulting in spillover of synaptic glutamate.…”

Section: Introductionmentioning

confidence: 99%

“…17,20 Ongoing research in both humans and animals are investigating restoring the glutamate and redox imbalance with N-acetylcysteine (NAC). [14][15][16]20 NAC is a cysteine prodrug and glutathione precursor, which enters glial cells in exchange for glutamate and is converted to intracellular glutathione, a potent antioxidant and neuroprotective substrate. NAC inhibits both the decrease in glutathione and withdrawal behaviors in an adult animal model of heroin dependence.…”

Section: Introductionmentioning

confidence: 99%

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N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats

et al. 2020

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BACKGROUND: Neonatal abstinence syndrome (NAS) is a significant problem. Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that N-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate. METHODS: Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days prior to delivery. Pups were randomized to receive either naloxone plus saline or NAC (50-100 mg/kg), administered on postnatal day (PND) 7. We performed MR spectroscopy on PND6-7 before, 30 min, and 120 min after withdrawal. On PND7, we assessed withdrawal behaviors for 90 min after naloxone administration and summed scores during peak withdrawal period. RESULTS: Mean summed behavioral scores were significantly different between groups (χ 2 (2) = 10.49, p = 0.005) but not different between NAC/NAL/OD and Sham (p = 0.14): SAL/NAL/OD = 17.2 ± 4.2 (n = 10); NAC/NAL/OD = 11.3 ± 5.6 (n = 9); Sham = 6.5 ± 0.6 (n = 4). SAL/NAL/OD pups had decreased glutathione at 120 min (p = 0.01), while NAC/NAL/OD pups maintained pre-withdrawal glutathione (p = 0.26). CONCLUSION: In antenatal OD, NAC maintains CNS glutathione and mitigates acute opioid withdrawal in neonatal rats. This is the first study to demonstrate acute opioid withdrawal neurochemical changes in vivo in neonatal OD. NAC is a potential novel treatment for NAS.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats

et al. 2020

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“…34 On the other hand, many studies indicated the involvement of the glutamatergic system in tolerance and dependence on opioids. [35][36][37] Some researchers have also showed that the pro-inflammatory cytokines, especially TNF-α through NF-κB inhibits the expression of Glutamate Carriers (GCs), especially the Glutamate-Aspartate (GLAST) vector, leading to increased neurotoxicity due to increases in synaptic glutamate levels. TNF-α promotes the expression of AMPA receptors in the CNS and also influences the activity of the glutamatergic nervous system.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Effects of Chronic Administration of Natural Honey on the Development of Dependence on Morphine in the Male Rats

2019

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Background: According to the previous studies, the exact mechanism of dependence on opioids and withdrawal syndrome has not been fully understood but one of the most important mechanisms is the increase of pro-inflammatory cytokines in CNS. On the other way, previous studies showed that natural honey (NHO) has anti-inflammatory properties. This study was aimed to evaluate the effects of chronic administration of natural honey on the development of morphine dependence in male rats. Methods: Honey was prepared from Tarom Oliya region in Zanjan province. Experiments were performed on male Wistar rats weighing 225-275 g, randomly divided into 6 groups (n=8). The study groups included morphine group, the three doses of morphine plus honey group (at doses of 200,400 and 800 mg/kg, i.p.), the morphine plus vehicle group, and the saline group. The subcutaneous injections of additive doses of morphine were used for 9 days to create morphine dependency. On the 9th day, one hour after the morning dose of morphine, naloxone (4 mg/kg, i.p.) was injected, and symptoms of withdrawal syndrome were assessed for 60 minutes. Then, blood samples were taken to measure TNF-α. One-way ANOVA and Tukey tests were used to compare the results. P- Value of <0.05 was considered as statistically significant. Results: The results of this study showed that intraperitoneal injection of honey at 3 doses (200, 400 and 800 mg/kg with p <0.001) could significantly decrease the total score of the symptoms compared to the morphine-vehicle control group. Natural honey (NHO) could significantly decrease TNF-α at dose of 400 mg/kg. Conclusion: The results indicated that chronic administration of NHO had beneficial effects in reducing symptoms of morphine withdrawal syndrome, and this effect is probably due to the anti-inflammatory effect caused by the polyphenolic compounds in honey.<br />

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“…Stimulation of these receptors increases dopamine release in the prefrontal cortex and induces feelings of euphoria in the user. 13 However, morphine can induce oxidative stress in organs such as the brain., 14 increase oxidative stress and neuronal apoptosis, destroy DNA, and produce reactive oxygen species. [14][15][16] Among the brain areas heavily affected by morphine is mesocorticolimbic and brain's prefrontal regions.…”

Section: Introductionmentioning

confidence: 99%

Effects of Royal Jelly on the Prefrontal Cortex in a Rat - Morphine Toxicity Model

Jalili

Roshankhah

Mohammadi

et al. 2019

J Apple Biotechnol Rep

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Introduction: Royal jelly (RJ) is a honey bee secretion with numerous medicinal properties and antioxidant activities. Morphine is a major risk factor in the development of functional disorders in several organ systems. This study was designed to evaluate the effects of RJ against morphineinduced damage to the prefrontal cortex of rats. Materials and Methods: In this study, 48 male Wistar rats were randomly assigned into 6 groups: sham group, morphine group, RJ groups (100, and 200 mg/kg), and morphine + RJ groups. Treatments were administered intraperitoneally and orally for 20 days on a daily basis. Ferric reducing/ antioxidant power (FRAP) method was applied to determine the total antioxidant capacity. The number of neurons and, dendritic spines were investigated by Golgi technique, and Griess technique was employed to determine the serum nitrite oxide level. Results: Morphine administration significantly increased the nitrite oxide level and total antioxidant capacity, and reduced neuronal dendritic spines and neurons compared to the sham group (P < 0.05). In all RJ and Morphine + RJ groups, the number of neurons and neuronal dendritic spines were elevated significantly, while nitrite oxide level and total antioxidant capacity were reduced compared to the morphine group (P < 0.05). Conclusions: RJ administration protected animals against oxidative stress and nitrite oxide. It also improves some prefrontal cortex parameters including number of neurons and dendritic spines because of the morphine.

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Bupropion attenuates morphine tolerance and dependence: Possible role of glutamate, norepinephrine, inflammation, and oxidative stress

Abstract: Bupropion efficacy in attenuation of morphine tolerance and dependence with its high safety and tolerability profile provide an alternative option to conventional agents e.g., ketamine and clonidine to modulate these phenomena.

Cited by 15 publications

References 52 publications

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats

Evaluating the Effects of Chronic Administration of Natural Honey on the Development of Dependence on Morphine in the Male Rats

Effects of Royal Jelly on the Prefrontal Cortex in a Rat - Morphine Toxicity Model

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