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Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice

Abstract

Methamphetamine (METH) abuse is a serious social and health problem worldwide. At present, there are no effective medications to treat METH addiction1. Here, we report that aggregated single-walled carbon nanotubes (aSWNTs) significantly inhibited METH self-administration, METH-induced conditioned place preference and METH- or cue-induced relapse to drug-seeking behaviour in mice. The use of aSWNTs alone did not significantly alter the mesolimbic dopamine system, whereas pretreatment with aSWNTs attenuated METH-induced increases in extracellular dopamine in the ventral striatum. Electrochemical assays suggest that aSWNTs facilitated dopamine oxidation. In addition, aSWNTs attenuated METH-induced increases in tyrosine hydroxylase or synaptic protein expression. These findings suggest that aSWNTs may have therapeutic effects for treatment of METH addiction by oxidation of METH-enhanced extracellular dopamine in the striatum.

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Figure 1: Effects of SWNTs on METH self-administration, cue-induced METH-seeking and METH-enhanced locomotion in mice.
Figure 2: Effects of SWNTs on METH-induced CPP, extinction of CPP and reinstatement of CPP.
Figure 3: Effects of SWNTs and METH on extracellular dopamine, dopamine oxidation and dopamine transporter (DAT) binding and function.
Figure 4: Effects of SWNTs and METH on the expression of tyrosine hydroxylase (TH) and the activities of dopamine degradation enzymes (MAO and COMT).
Figure 5: Effects of METH and SWNTs on synaptic marker proteins and synaptic density in the striatum.

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Acknowledgements

This work was supported by the National Key Scientific Project for New Drug Discovery and Development (2013ZX09301305), the National Natural Science Foundation key project (31430031), the National Distinguished Young Scholars grant (31225009) and the National Natural Science Foundation (No. 81373383) in China. This work was also supported by State High-Tech Development Plan (2012AA020804 and SS2014AA020708) and the National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), National Institutes of Health (NIH) in the United States of America. We also gratefully acknowledge support from the Chinese Academy of Sciences (CAS), Hundred Talents Program (07165111ZX), the CAS Knowledge Innovation Program, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA09030301) and the external collaboration program of BIC, Chinese Academy of Science (121D11KYSB20130006). We thank I. Hanson for English editing services.

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X.X., J.-Y.Y., Y.H., G.-L.G., Z.-X.X., C.-F.W. and X.-J.L. conceived and designed the experiments. X.X., Y.H., L.-R.W., P.L., L.-S.Y., G.-H.B., M.-M.Z., Y.-Y.L., X.-T.Y., X.-Y.F., X.-M.W. and W.C. performed the experiments. X.X., J.-Y.Y., Y.H., L.-R.W., R.-W.X., J.Q., H.-J.Z., Z.-X.X. and X.-J.L. analyzed the data. X.X. and L.-R.W. contributed materials/analysis tools. X.X., J.-Y.Y., Y.H., T.W., Z.-X.X. C.-F.W. and X.-J.L. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Zheng-Xiong Xi, Chun-Fu Wu or Xing-Jie Liang.

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Xue, X., Yang, JY., He, Y. et al. Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice. Nature Nanotech 11, 613–620 (2016). https://doi.org/10.1038/nnano.2016.23

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