Neurochemical Research

, Volume 44, Issue 4, pp 874–883 | Cite as

Morphine Dependence is Attenuated by Treatment of 3,4,5-Trimethoxy Cinnamic Acid in Mice and Rats

  • Sohyeon Moon
  • Seungmin Kang
  • Heeyeon Shin
  • Taddesse Yayeh
  • Bongjun Sur
  • Seikwan OhEmail author
Original Paper


The effect of 3, 4, 5-trimethoxy cinnamic acid (TMCA) against morphine-induced dependence in mice and rats was investigated. Mice were pretreated with TMCA and then morphine was injected intraperitoneally; whereas rats were treated with TMCA (i.p.) and infused with morphine into the lateral ventricle of brain. Naloxone-induced morphine withdrawal syndrome and conditioned place preference test were performed. Moreover, western blotting and immunohistochemistry were used to measure protein expressions. Number of naloxone-precipitated jumps and conditioned place preference score in mice were attenuated by TMCA. Likewise, TMCA attenuated morphine dependent behavioral patterns such as diarrhea, grooming, penis licking, rearing, teeth chattering, and vocalization in rats. Moreover, the expression levels of pNR1and pERK in the frontal cortex of mice and cultured cortical neurons were diminished by TMCA. In the striatum, pERK expression was attenuated despite unaltered expression of pNR1 and NR1. Interestingly, morphine-induced elevations of FosB/ΔFosB+ cells were suppressed by TMCA (50, 100 mg/kg) in the nucleus accumbens sub-shell region of mice. In conclusion, TMCA could be considered as potential therapeutic agent against morphine-induced dependence.


3, 4, 5-Trimethoxy cinnamic acid (TMCA) Morphine dependence NMDA Nucleus accumbens FosB 



This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Ministry of Science, ICT & Future Planning (MRC, 2010-0029355).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sohyeon Moon
    • 1
  • Seungmin Kang
    • 1
  • Heeyeon Shin
    • 2
  • Taddesse Yayeh
    • 3
  • Bongjun Sur
    • 1
  • Seikwan Oh
    • 1
    Email author
  1. 1.Department of Molecular Medicine, School of MedicineEwha Womans UniversitySeoulRepublic of Korea
  2. 2.St. Louis College of PharmacySt. LouisUSA
  3. 3.Department of Veterinary Medicine, School of Animal and Veterinary MedicineBahir Dar UniversityBahir DarEthiopia

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