Valproate attenuates the development of morphine antinociceptive tolerance

Dobashi, Tamae; Tanabe, Serabi; Jin, Hisayo; Nishino, Takashi; Aoe, Tomohiko

doi:10.1016/j.neulet.2010.08.084

Cited by 21 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, our in vitro data showed that morphine induces ER stress-mediated defective autophagy which, in turn, leads to astrocyte activation and secretion of proinflammatory cytokines. The role of morphine-mediated activation of ER stress has been reported previously in the in vivo morphine tolerance [82,83]. …”

Section: Discussionmentioning

confidence: 88%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

View full text Add to dashboard Cite

A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR). In vivo validation demonstrated preferential activation of ER stress/autophagy axis in the areas of the brain not associated with pain such as the basal ganglia, frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus macaques, and this correlated with increased astrocyte activation and neuroinflammation. Interventions aimed at blocking either the MOR or ER stress could thus likely be developed as promising therapeutic targets for abrogating morphine-mediated astrocytosis.

show abstract

Section: Discussionmentioning

confidence: 88%

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Significant individual or interactive effects of morphine were not detected at 4 h. Thus, based on the time-dependent effects of opiates observed by others (Dobashi et al, 2010; Xie et al, 2010), we examined HIV + sup and morphine-mediated effects at longer time intervals (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…However, other studies have disagreed on whether opiates induce GSK3β activation (Dobashi et al, 2010; Xie et al, 2010) or inactivation (Li et al, 2010; Polakiewicz et al, 1998); this may be because the effects of opiates on GSK3β-activity occur in a dose- and time-dependent manner (Xie et al, 2010). Acute activation of MORs tends to inhibit GSK3β activity via PI3K/Akt signaling pathway (Polakiewicz et al, 1998), while chronic activation of MORs tends to elevate GSK3β activity (Dobashi et al, 2010; Xie et al, 2010), perhaps through increased intracellular calcium (Dobashi et al, 2010; Hartigan and Johnson, 1999; Quillan et al, 2002). In accord with these studies, our results also show that morphine exerts time-dependent effects on GSK3β activation (Figs.…”

Section: Discussionmentioning

confidence: 99%

GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity

Masvekar

El‐Hage

Hauser

et al. 2015

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Infection of the CNS with HIV-1 occurs rapidly after primary peripheral infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders. Our previous work has shown that the selected neurotoxic effects induced by individual viral proteins, Tat and gp120, and by HIV+ supernatant are enhanced by co-exposure to morphine. This mimics co-morbid neurological effects observed in opiate-abusing HIV+ patients. Although there is a correlation between opiate drug abuse and progression of HIV-1-associated neurocognitive disorders, the mechanisms underlie interactions between HIV-1 and opiates remain obscure. Previous studies have shown that HIV-1 induces neurotoxic effects through abnormal activation of GSK3β. Interestingly, expression of GSK3β has shown to be elevated in brains of young opiate abusers indicating that GSK3β is also linked to neuropathology seen with opiate abusing patients. Thus, we hypothesize that GSK3β activation is a point of convergence for HIV- and opiate-mediated interactive neurotoxic effects. Neuronal cultures were treated with supernatant from HIV-1SF162-infected THP-1 cells, in the presence or absence of morphine and GSK3β inhibitors. Our results show that GSK3β inhibitors, including valproate and small molecule inhibitors, significantly reduce HIV-1-mediated neurotoxic outcomes, and also negate interactions with morphine that result in cell death, suggesting that GSK3β-activation is an important point of convergence and a potential therapeutic target for HIV- and opiate-mediated neurocognitive deficits.

show abstract

“…In this study, TDZD-8, a selective GSK-3β inhibitor, attenuated remifentanil-induced thermal and mechanical hyperalgesia in rats. Morphine treatment increased GSK-3β activity in mice, and GSK-3β inhibitors prevent the development of tolerance[21,40]. Convincing evidence show that AR-A014418, a selective GSK-3β inhibitor, produces antihyperalgesia and antinociception in neuropathic pain model in mice[41,42].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Glycogen Synthase Kinase-3β Prevents Remifentanil-Induced Hyperalgesia via Regulating the Expression and Function of Spinal N-Methyl-D-Aspartate Receptors In Vivo and Vitro

Wang

Xie

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

A large number of experimental and clinical studies have confirmed that brief remifentanil exposure can enhance pain sensitivity presenting as opioid-induced hyperalgesia (OIH). N-methyl-D-aspartate (NMDA) receptor antagonists have been reported to inhibit morphine analgesic tolerance in many studies. Recently, we found that glycogen synthase kinase-3β (GSK-3β) modulated NMDA receptor trafficking in a rat model of remifentanil-induced postoperative hyperalgesia. In the current study, it was demonstrated that GSK-3β inhibition prevented remifentanil-induced hyperalgesia via regulating the expression and function of spinal NMDA receptors in vivo and in vitro. We firstly investigated the effects of TDZD-8, a selective GSK-3β inhibitor, on thermal and mechanical hyperalgesia using a rat model of remifentanil-induced hyperalgesia. GSK-3β activity as well as NMDA receptor subunits (NR1, NR2A and NR2B) expression and trafficking in spinal cord L4-L5 segments were measured by Western blot analysis. Furthermore, the effects of GSK-3β inhibition on NMDA-induced current amplitude and frequency were studied in spinal cord slices by whole-cell patch-clamp recording. We found that remifentanil infusion at 1 μg·kg-1·min-1 and 2 μg·kg-1·min-1 caused mechanical and thermal hyperalgesia, up-regulated NMDA receptor subunits NR1 and NR2B expression in both membrane fraction and total lysate of the spinal cord dorsal horn and increased GSK-3β activity in spinal cord dorsal horn. GSK-3β inhibitor TDZD-8 significantly attenuated remifentanil-induced mechanical and thermal hyperalgesia from 2 h to 48 h after infusion, and this was associated with reversal of up-regulated NR1 and NR2B subunits in both membrane fraction and total lysate. Furthermore, remifentanil incubation increased amplitude and frequency of NMDA receptor-induced current in dorsal horn neurons, which was prevented with the application of TDZD-8. These results suggest that inhibition of GSK-3β can significantly ameliorate remifentanil-induced hyperalgesia via modulating the expression and function of NMDA receptors, which present useful insights into the mechanistic action of GSK-3β inhibitor as potential anti-hyperalgesic agents for treating OIH.

show abstract

Valproate attenuates the development of morphine antinociceptive tolerance

Cited by 21 publications

References 24 publications

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis

GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity

Inhibition of Glycogen Synthase Kinase-3β Prevents Remifentanil-Induced Hyperalgesia via Regulating the Expression and Function of Spinal N-Methyl-D-Aspartate Receptors In Vivo and Vitro

Contact Info

Product

Resources

About