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

Toll-like receptor 3 modulates the behavioral effects of cocaine in mice.
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Zhu R, Bu Q, Fu D, Shao X, Jiang L, Guo W, Chen B, Liu B, Hu Z, Tian J, Zhao Y, Cen X,


Zhu R, Bu Q, Fu D, Shao X, Jiang L, Guo W, Chen B, Liu B, Hu Z, Tian J, Zhao Y, Cen X, (click to view)

Zhu R, Bu Q, Fu D, Shao X, Jiang L, Guo W, Chen B, Liu B, Hu Z, Tian J, Zhao Y, Cen X,

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Journal of neuroinflammation 2018 03 2315(1) 93 doi 10.1186/s12974-018-1130-8
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 TLR3mice. 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 TLR3mice 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.

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