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

Autor: Nguyen PT; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea., Shin EJ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea., Dang DK; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea., Tran HQ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea., Jang CG; Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea., Jeong JH; Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea., Lee YJ; Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea., Lee HJ; Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea., Lee YS; Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea., Yamada K; Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan., Nabeshima T; Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Toyoake 470-1192, Japan; Aino University, Ibaraki, Osaka 567-0012, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya 468-0069, Japan., Kim HC; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2018 Feb; Vol. 113, pp. 69-84. Date of Electronic Publication: 2017 Dec 02.
DOI: 10.1016/j.neuint.2017.11.017
Abstrakt: 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.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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