Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells

Desjardins, Stephane; Belkaï, Emilie; Crété, Dominique; Cordonnier, L.; Scherrmann, Jean‐Michel; Noble, Florence; Marie-Claire, Cynthia

doi:10.1016/j.neuropharm.2008.08.027

Cited by 30 publications

(50 citation statements)

References 45 publications

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“…Therefore, we cannot rule out that other pro-apoptotic neurotrophins could be released during morphine withdrawal and be involved in its neurotoxic effects. In addition, withdrawal from morphine can positively affect the production of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α, and negatively affect the production of anti-inflammatory cytokines such as CCL5 (Campbell et al 2013; Desjardins et al 2008; Eisenstein et al 2006; Hutchinson et al 2011). Likewise, withdrawal can increase susceptibility to outside pathogens (Eisenstein et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Morphine Withdrawal Increases Brain-Derived Neurotrophic Factor Precursor

et al. 2017

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Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of morphine withdrawal on BDNF and its precursor protein, or proBDNF, which induces neuronal apoptosis. In this work, we examined whether BDNF and proBDNF levels change in rats chronically injected with escalating doses of morphine and those who undergo spontaneous withdrawal for 60 hr. We observed, in the frontal cortex and striatum, that the ratio of BDNF to proBDNF changed depending upon the experimental paradigm. Morphine treatment and morphine withdrawal increased both BDNF and proBDNF levels. However, the increase in proBDNF immunoreactivity in withdrawal rats was more robust than that observed in morphine-treated rats. proBDNF is processed either intracellularly by furin or extracellularly by the tissue plasminogen activator (tPA)/plasminogen system or matrix metalloproteases (MMPs). To examine the mechanisms whereby chronic morphine treatment and morphine withdrawal differentially affects BDNF/proBDNF, the levels MMP-3 and -7, furin, and tPA were analyzed. We found that morphine increases tPA levels whereas withdrawal causes a decrease. To confirm the involvement of tPA in the morphine-mediated effect on BDNF/proBDNF, we exposed cortical neurons to morphine in the presence of the tPA inhibitor PAI-1. This inhibitor reversed the morphine-mediated decrease in proBDNF, supporting the hypothesis that morphine increases the availability of BDNF by promoting the extracellular processing of proBDNF by tPA. Because proBDNF could negatively influence synaptic repair, preventing withdrawal is crucial for reducing neurotoxic mechanisms associated with opioid abuse.

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Section: Discussionmentioning

confidence: 99%

Morphine Withdrawal Increases Brain-Derived Neurotrophic Factor Precursor

et al. 2017

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“…Male Sprague Dawley rats (16 -18 d old) were treated with morphine according to procedures described previously (Desjardins et al, 2008). Briefly, morphine dependence was induced in rats by repeated intraperitoneal injections of morphine twice daily at 8:00 A.M. and 7:00 P.M. Morphine doses were progressively increased from 10 to 40 mg/kg: first day, 2 ϫ 10 mg/kg; second day, 2 ϫ 20 mg/kg; third day, 2 ϫ 30 mg/kg; fourth and fifth days, 2 ϫ 40 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Chronic Morphine Treatment Switches the Effect of Dopamine on Excitatory Synaptic Transmission from Inhibition to Excitation in Pyramidal Cells of the Basolateral Amygdala

Luan²,

Chen³

et al. 2011

J. Neurosci.

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Dopaminergic signaling in the basolateral amygdala (BLA) is important for drug-stimulus learning that triggers relapse to drug-seeking behavior. However, little is known about adaptive changes in this signaling pathway upon chronic morphine treatment. In this paper, we observed the influence of chronic morphine treatment on the effect of dopamine (DA) on the excitatory transmission in the pyramidal cells of BLA in slices with the whole-cell patch-clamp method. We also studied its mechanism and significance with pharmacological approaches combined with biochemical and behavioral techniques. The results showed that chronic morphine exposure switched the effect of DA on the excitatory synaptic transmission from inhibition to excitation; the chronic morphine-induced switching action on the effect of DA was due to its influence on D1 receptors; the site of the effect of chronic morphine treatment on D1 receptors was at presynaptic locus; chronic morphine treatment induced a significant increase in the amount of D1 receptor expression in the synaptosomes and synaptosomal membrane fraction from BLA; the enhancement of presynaptic glutamate release by D1 receptor agonist upon chronic morphine treatment was dependent on the activation of cAMP-dependent protein kinase; and the intra-BLA injection of D1 receptor antagonist canceled the conditioned place aversion (CPA) in morphine-dependent rats. In conclusion, chronic morphine treatment switches the effect of DA on the excitatory synaptic transmission from inhibition to excitation by the presynaptic D1 receptor amount increase-mediated glutamate release in the pyramidal cells of BLA and the blockade of D1 receptors in BLA cancels CPA in morphine-dependent rats.

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“…We previously showed that P-gp and Bcrp were upregulated in brain microvessels not before 12 h after the suspension of the morphine treatment (day 5). 11 Interestingly, the onset of the registered induction coincided with the initial development of an opioid withdrawal syndrome in the rat, 22 suggesting that these two phenomena could be mechanistically related. Furthermore, we showed that morphine-mediated P-gp and Bcrp upregulation depended on the activation of the NMDA glutamatergic receptor and COX-2 activity.…”

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confidence: 98%

“…The development of a spontaneous withdrawal syndrome in study 2 was previously described by our research team. 22 Here, we described behavioral signs using the same morphine protocol after the precipitation of opioid withdrawal with the injection of the mreceptor antagonist naloxone. Animals showed typical opioid withdrawal behavioral signs, including abnormal posture, diarrhea, mastication, wet-dog shakes, ptosis, salivation, and jumping.…”

mentioning

confidence: 99%

“…This peak and trough plasma morphine alternation is favorable to the installation of physical dependence and withdrawal once morphine treatment is suspended. 22 To test the effect of a strong precipitated morphine withdrawal on P-gp and Bcrp expressions, we applied study 2 and dosed rats with naloxone, a strong inducer of morphine withdrawal, after the last morphine injection. The protocol adopted for study 3 contrasts with study 2 by having an additional spontaneous withdrawal over a 2-day period, which increased the naloxone-precipitated withdrawal syndrome.…”

mentioning

confidence: 99%

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