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

Publication date: Available online 2 December 2017 Source:Neurochemistry International Author(s): 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 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 a...
Source: Neurochemistry International - Category: Neuroscience Source Type: research