Morphine Addiction and Oxidative Stress: The Potential Effects of Thioredoxin-1.

Xian-Si Zeng,Zhan-Qi Wang,Jin-Jing Jia,Wen-Shuo Geng

doi:10.3389/fphar.2020.00082

Xian-Si Zeng, Zhan-Qi Wang + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2020.00082

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Abstract

Long-term administration of morphine for the management of chronic pain will result in tolerance to its analgesic effect and could even cause drug dependence. Numerous studies have demonstrated significant redox alteration in morphine dependence and addiction. Thioredoxin-1 (Trx-1) play important roles in controlling the cellular redox balance. In recent years, several recent studies have demonstrated that Trx-1 may be a promising novel therapeutic target for morphine addiction. In this article, we firstly review the redox alteration in morphine addiction. We also summarize the expression and the protective roles of Trx-1 in morphine dependence. We further highlight the protection of geranylgeranylacetone (GGA), a noncytotoxic pharmacological inducer of Trx-1, in morphine-induced conditioned place preference. In conclusion, Trx-1 may be very promising for clinical therapy of morphine addiction in the future.

Highlights

Morphine, the most effective opioid analgesic, is clinically used for severe acute and chronic pain
Li et al further clarified that Trx-1 overexpression in transgenic mice inhibited morphine-induced conditioned place preference (CPP) through upregulating the endogenous concentration of g-aminobutyric acid (GABA) and the expression of GABAB receptor in the ventral tegmental area (VTA) and nucleus accumbens (NAc) (Li et al, 2018) (Table 2)
GGA inhibited reinstatement of morphine-induced CPP through strengthening the expression of Trx-1 and regulating the N-methyl d-aspartate receptor 2B subunit (NR2B)/extracellular signal-regulated kinase (ERK) pathway in the NAc and Hipp, a brain region participating in associative processes such as declarative memory (Guo et al, 2018) (Table 2), suggesting that GGA may be a promising therapeutic drug for morphine-induced relapse

Summary

Introduction

The most effective opioid analgesic, is clinically used for severe acute and chronic pain. Curcumin lowered the increased lipid peroxidation and mitochondrial GSSG (oxidized GSH) levels in morphine-treated rats (Motaghinejad et al, 2015a) and attenuated morphine tolerance and dependence by inhibiting the activity of Ca2+/calmodulin-dependent protein kinase II a (Hu et al, 2015).

Results

Conclusion