TY - JOUR
T1 - Role of dopamine D1 receptor in 3-fluoromethamphetamine-induced neurotoxicity in mice
AU - Nguyen, Phuong Tram
AU - Shin, Eun Joo
AU - Dang, Duy Khanh
AU - Tran, Hai Quyen
AU - Jang, Choon Gon
AU - Jeong, Ji Hoon
AU - Lee, Yu Jeung
AU - Lee, Hyo Jong
AU - Lee, Yong Sup
AU - Yamada, Kiyofumi
AU - Nabeshima, Toshitaka
AU - Kim, Hyoung Chun
N1 - Funding Information:
This study was supported by a grant ( 14182MFDS979 ) from the Korea Food and Drug Administration , by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (# NRF-2017R1A2B1003346 ), Republic of Korea, and by a grant ( 17H04252 ) from the Japan Society for the Promotion of Science (JSPS) . Phuong-Tram Nguyen, Duy-Khanh Dang and Hai-Quyen Tran were supported by the BK21 PLUS program, National Research Foundation of Korea , Republic of Korea. Equipment at the Institute of New Drug Development Research (Kangwon National University) was used for this study. The English in this document has been checked by at least two professional editors, both native speakers of English.
Publisher Copyright:
© 2017
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuint.2017.11.017
DO - 10.1016/j.neuint.2017.11.017
M3 - Article
C2 - 29197543
AN - SCOPUS:85036557418
VL - 113
SP - 69
EP - 84
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
ER -