Abstract
Methamphetamine (Meth), a commonly used central nervous system stimulant, is highly addictive. Currently, there is no effective treatment for Meth dependence and abuse, although cell adhesion molecules (CAMs) have been shown to play an important role in the formation and remodeling of synapses in the nervous system while also being involved in addictive behavior. Contactin 1 (CNTN1) is a CAM that is widely expressed in the brain; nevertheless, its role in Meth addiction remains unclear. Therefore, in the present study, we established mouse models of single and repeated Meth exposure and subsequently determined that CNTN1 expression in the nucleus accumbens (NAc) was upregulated in mice following single or repeated Meth exposure, whereas CNTN1 expression in the hippocampus was not significantly altered. Intraperitoneal injection of the dopamine receptor 2 antagonist haloperidol reversed Meth-induced hyperlocomotion and upregulation of CNTN1 expression in the NAc. Additionally, repeated Meth exposure also induced conditioned place preference (CPP) in mice and upregulated the expression levels of CNTN1, NR2A, NR2B, and PSD95 in the NAc. Using an AAV-shRNA-based approach to specifically silence CNTN1 expression in the NAc via brain stereotaxis reversed Meth-induced CPP and decreased the expression levels of NR2A, NR2B, and PSD95 in the NAc. These findings suggest that CNTN1 expression in the NAc plays an important role in Meth-induced addiction, and the underlying mechanism may be related to the expression of synapse-associated proteins in the NAc. The results of this study improved our understanding of the role of cell adhesion molecules in Meth addiction.
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All the data generated or analyzed during this study are included in this published article; further inquiries can be directed to the corresponding authors.
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We wish to thank you for the research instrument support provided by Central South University and thank Editage (www.editage.cn) for English language editing.
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This research was supported by National Natural Science Foundation of China (81471372), the Natural Science Foundation of Hunan Province (2019JJ40369, 2018JJ3635) and Graduate Research and Innovation Projects of Central South University (2022zzts0924).
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F.L and C.Q.L. conceived the study, designed experiments and provided funds. L.X.Z, X.Y.L and M.Q.L. performed experiments and analyzed the results. J.Y.Y and G.J.Z performed the analysis of Western Blotting. Z.R.C and Q.L. performed the analysis of Immunohistochemistry and microscopy images. L.X.Z. and Z.H.Z. wrote the main manuscript. All authors reviewed and edited the manuscript.
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Zhang, L., Zeng, Z., Lu, X. et al. CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice. Neurotox Res 41, 324–337 (2023). https://doi.org/10.1007/s12640-023-00640-9
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DOI: https://doi.org/10.1007/s12640-023-00640-9