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NCAM Signaling Mediates the Effects of GDNF on Chronic Morphine-Induced Neuroadaptations

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Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for midbrain dopamine (DA) neurons, while the DA neurons in the ventral tegmental area (VTA) is a crucial part of the neural circuits associated with drug addiction. Recently, more and more evidence suggests that GDNF plays an important role in negatively regulating the neuroadaptations induced by chronic exposure to drugs, which was thought to be the neurobiological basis of drug addiction, but the underlying mechanism is still unknown. More recently, the neural cell adhesion molecule (NCAM), which plays an important role in the process of neural plasticity, has been identified as an alternative signaling receptor for GDNF. The purpose of this study was to investigate whether NCAM was involved in the effects of GDNF on the neuroadaptations induced by chronic morphine exposure. Immunostaining results showed that NCAM was widely expressed in the VTA of rats, including all the DA neurons. The results also showed that the phosphorylation of NCAM-associated FAK, but not the total NCAM, was upregulated by GDNF, and this upregulation was inhibited by pre-treatment with the NCAM function-blocking antibody. Moreover, pre-treatment with the antibody could antagonize the effect of GDNF on inhibiting the neuroadaptations induced by chronic morphine exposure, including the decreases of the number and length of neurites and the size of cell bodies of VTA dopamine neurons, as well as the increase of tyrosine hydroxylase in the VTA dopamine neurons. These results suggest that NCAM signaling is involved in the negative regulatory effects of GDNF on chronic morphine-induced neuroadaptations.

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Abbreviations

GDNF:

Glial cell line-derived neurotrophic factor

NCAM:

Neural cell adhesion molecule

FAK:

Focal adhesion kinase

VTA:

Ventral tegmental area

DA:

Dopamine

TH:

Tyrosine hydroxylase

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Acknowledgments

This project was supported by grants from the National Natural Science of China (30900417 and 30901402) and the Educational Department Science Research Foundation of Jiangsu Province (08KJB180011 and 09KJD320008). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China

    Li Li, Junping Cao, Suming Zhang, Cunjin Wang, Jinfeng Wang, Ge Song, Hongjun Wang & Licai Zhang

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  1. Li Li
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  2. Junping Cao
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  3. Suming Zhang
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  4. Cunjin Wang
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  6. Ge Song
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  7. Hongjun Wang
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  8. Licai Zhang
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Correspondence to Junping Cao.

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Li Li Junping Cao, and Suming Zhang contributed equally to this work.

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Li, L., Cao, J., Zhang, S. et al. NCAM Signaling Mediates the Effects of GDNF on Chronic Morphine-Induced Neuroadaptations. J Mol Neurosci 53, 580–589 (2014). https://doi.org/10.1007/s12031-013-0224-0

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  • DOI: https://doi.org/10.1007/s12031-013-0224-0

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