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

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