Glutathione peroxidase-1 knockout potentiates behavioral sensitization induced by cocaine in mice via σ-1 receptor-mediated ERK signaling: A comparison with the case of glutathione peroxidase-1 overexpressing transgenic mice
- Authors
- Mai, H.N.; Pham, D.T.; Chung, Y.H.; Sharma, N.; Cheong, J.H.; Yun, J.; Nah, S.-Y.; Jeong, J.H.; Gen, Lei X.; Shin, E.-J.; Nabeshima, T.; Kim, H.-C.
- Issue Date
- Nov-2020
- Publisher
- Elsevier Inc.
- Keywords
- Behavioral sensitization; Cocaine; Glutathione peroxidase-1 gene; Nrf-2-related system; Phospho-ERK; Sigma (σ)-1 receptor
- Citation
- Brain Research Bulletin, v.164, pp 107 - 120
- Pages
- 14
- Journal Title
- Brain Research Bulletin
- Volume
- 164
- Start Page
- 107
- End Page
- 120
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/43814
- DOI
- 10.1016/j.brainresbull.2020.08.011
- ISSN
- 0361-9230
1873-2747
- Abstract
- We demonstrated that the gene of glutathione peroxidase-1 (GPx-1), a major antioxidant enzyme, is a potential protectant against the neurotoxicity and conditioned place preference induced by cocaine. Because the sigma (σ)-1 receptor is implicated in cocaine-induced drug dependence, we investigated whether the GPx-1 gene modulates the σ-1 receptor in the behavioral sensitization induced by cocaine. Cocaine-induced behavioral sensitization was more pronounced in GPx-1 knockout (KO) than wild-type (WT) mice and was less pronounced in GPx-1 overexpressing transgenic (GPx-1 TG) than non-TG mice. Cocaine treatment significantly enhanced the oxidative burden and reduced the GSH levels in the striatum of WT, GPx-1 KO, and non-TG mice but not in that of GPx-1 TG mice. In addition, cocaine significantly increased the nuclear translocation, its DNA binding activity of nuclear factor erythroid-2-related factor 2 (Nrf2) as well as the mRNA expression of γ-glutamylcysteine (GCL). The genetic depletion of GPx-1 inhibited the Nrf2-related glutathione system, whereas the genetic overexpression of GPx-1 activated this system against behavioral sensitization. BD1047, a σ-1 receptor antagonist, and U0126, an ERK inhibitor significantly induced the Nrf2-related antioxidant potential against behavioral sensitization. Unlike BD1047, U0126 did not affect the cocaine-induced σ-1 receptor immunoreactivity, suggesting that the σ-1 receptor is an upstream molecule for ERK signaling. Importantly, BD1047 and U0126 failed to affect the σ-1 receptor immunoreactivity and ERK phosphorylation induced by cocaine in GPx-1 TG mice. Our results suggest that GPx-1 is a critical mediator for the attenuation of cocaine-induced behavioral sensitization via modulating σ-1 receptor-mediated ERK activation by the induction of the Nrf2-related system. © 2020 Elsevier Inc.
- Files in This Item
-
- Appears in
Collections - College of Medicine > College of Medicine > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.