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Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

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Abstract

Clinical and animal studies have indicated that propofol has potential for abuse, but the specific neurobiological mechanism underlying propofol reward is not fully understood. The purpose of this study was to investigate the role of extracellular signal-regulated kinase (ERK) signal transduction pathways in the nucleus accumbens (NAc) in propofol self-administration. We tested the expression of p-ERK in the NAc following the maintenance of propofol self-administration in rats. We also assessed the effect of administration of SCH23390, an antagonist of the D1 dopamine receptor, on the expression of p-ERK in the NAc in propofol self-administering rats, and examined the effects of intra-NAc injection of U0126, an MEK inhibitor, on propofol reinforcement in rats. The results showed that the expression of p-ERK in the NAc increased significantly in rats maintained on propofol, and pre-treatment with SCH23390 inhibited the propofol self-administration and diminished the expression of p-ERK in the NAc. Moreover, intra-NAc injection of U0126 (4 µg/side) attenuated the propofol self-administration. The data suggest that ERK signal transduction pathways coupled with D1 dopamine receptors in the NAc may be involved in the maintenance of propofol self-administration and its rewarding effects.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (81271469 and 81471350), the Natural Science Foundation of Zhejiang Province, China (Z2101211 and Y20140692), and a Medical Health Project of Zhejiang Province, China (2014KYB161).

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

    Benfu Wang, Xiaowei Yang, Sicong Wang, Wenxuan Lin & Qingquan Lian

  2. Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo, 315010, China

    Anna Sun, Miaojun Lai, Huaqiang Zhu & Wenhua Zhou

  3. Department of Infection and Liver Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

    Lanman Xu

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  1. Benfu Wang
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  2. Xiaowei Yang
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  3. Anna Sun
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Correspondence to Wenhua Zhou or Qingquan Lian.

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Wang, B., Yang, X., Sun, A. et al. Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats. Neurosci. Bull. 32, 531–537 (2016). https://doi.org/10.1007/s12264-016-0066-1

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  • DOI: https://doi.org/10.1007/s12264-016-0066-1

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