Role of dopamine D1 receptor in 3-fluoromethamphetamine-induced neurotoxicity in mice

Phuong Tram Nguyen, Eun Joo Shin, Duy Khanh Dang, Hai Quyen Tran, Choon Gon Jang, Ji Hoon Jeong, Yu Jeung Lee, Hyo Jong Lee, Yong Sup Lee, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

研究成果: Article

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3-Fluoromethamphetamine (3-FMA) is an illegal designer drug of methamphetamine (MA) derivative. Up to date, little is known about the neurotoxic potential of 3-FMA. In the present study, we investigated the role of dopamine receptors in neurotoxicity induced by 3-FMA in comparison with MA (35 mg/kg, i.p.) as a control drug. Here we found that 3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. Treatment with 3-FMA (40 mg/kg, i.p.) resulted in significant hyperthermia, oxidative stress and microgliosis (microglial differentiation into M1 phenotype) followed by pro-apoptotic changes and the induction of terminal deoxynucleotidyl transferase dUDP nick end labeling (TUNEL)-positive cells. Moreover, 3-FMA significantly produced dopaminergic impairments [i.e., increase in dopamine (DA) turnover rate and decreases in DA level, and in the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2)] with behavioral impairments. These dopaminergic neurotoxic effects of 3-FMA were comparable to those of MA. SCH23390, a dopamine D1 receptor antagonist, but not sulpiride, a dopamine D2 receptor antagonist significantly attenuated 3-FMA-induced neurotoxicity. Although both SCH23390 and sulpiride attenuated MA-induced dopaminergic neurotoxicity, sulpiride is more effective than SCH23390 on the dopaminergic neurotoxicity. Interestingly, SCH23390 treatment positively modulated 3-FMA-induced microglial activation (i.e., SCH23390 inhibited M1 phenotype from 3-FMA insult, but activated M2 phenotype). Therefore, our results suggest that the activation of dopamine D1 receptor is critical to 3-FMA-induced neurotoxicity, while both dopamine D1 and D2 receptors (dopamine D2 receptor > dopamine D1 receptor) mediate MA-induced dopaminergic neurotoxicity.

元の言語English
ページ(範囲)69-84
ページ数16
ジャーナルNeurochemistry International
113
DOI
出版物ステータスPublished - 01-02-2018

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

これを引用

Nguyen, P. T., Shin, E. J., Dang, D. K., Tran, H. Q., Jang, C. G., Jeong, J. H., Lee, Y. J., Lee, H. J., Lee, Y. S., Yamada, K., Nabeshima, T., & Kim, H. C. (2018). Role of dopamine D1 receptor in 3-fluoromethamphetamine-induced neurotoxicity in mice. Neurochemistry International, 113, 69-84. https://doi.org/10.1016/j.neuint.2017.11.017