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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Toll-like receptor 3 modulates the behavioral effects of cocaine in mice

Authors: Ruiming Zhu, Qian Bu, Dengqi Fu, Xue Shao, Linhong Jiang, Wei Guo, Bo Chen, Bin Liu, Zhengtao Hu, Jingwei Tian, Yinglan Zhao, Xiaobo Cen

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

The nucleus accumbens in the midbrain dopamine limbic system plays a key role in cocaine addiction. Toll-like receptors (TLRs) are important pattern-recognition receptors (PPRs) in the innate immune system that are also involved in drug dependence; however, the detailed mechanism is largely unknown.

Methods

The present study was designed to investigate the potential role of TLR3 in cocaine addiction. Cocaine-induced conditioned place preference (CPP), locomotor activity, and self-administration were used to determine the effects of TLR3 in the rewarding properties of cocaine. Lentivirus-mediated re-expression of Tlr3 (LV-TLR3) was applied to determine if restoration of TLR3 expression in the NAc is sufficient to restore the cocaine effect in TLR3−/− mice. The protein levels of phospho-NF-κB p65, IKKβ, and p-IκBα both in the cytoplasm and nucleus of cocaine-induced CPP mice were detected by Western blot.

Results

We showed that both TLR3 deficiency and intra-NAc injection of TLR3 inhibitors significantly attenuated cocaine-induced CPP, locomotor activity, and self-administration in mice. Importantly, the TLR3−/− mice that received intra-NAc injection of LV-TLR3 displayed significant increases in cocaine-induced CPP and locomotor activity. Finally, we found that TLR3 inhibitor reverted cocaine-induced upregulation of phospho-NF-κB p65, IKKβ, and p-IκBα.

Conclusions

Taken together, our results describe that TLR3 modulates cocaine-induced behaviors and provide further evidence supporting a role for central pro-inflammatory immune signaling in drug reward. We propose that TLR3 blockade could be a novel approach to treat cocaine addiction.
Appendix
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Metadata
Title
Toll-like receptor 3 modulates the behavioral effects of cocaine in mice
Authors
Ruiming Zhu
Qian Bu
Dengqi Fu
Xue Shao
Linhong Jiang
Wei Guo
Bo Chen
Bin Liu
Zhengtao Hu
Jingwei Tian
Yinglan Zhao
Xiaobo Cen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1130-8

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