Abstract
1822
Objectives 3, 4-methylenedioxymethamphetamine (MDMA) has been shown to induce serotonergic neurotoxicity and increase autophagy-related protein 5 expression in the cells. The 3-Methyladenine (3-MA) is an autophagic regulator that is responsible for the turnover of proteins or organelles through lysosomal degradation for the neural homeostasis. In this study, we used 4-[18F]-ADAM (a serotonin transporter imaging agent) coupled with small animal-PET to investigate the neuroprotective effects of 3-MA against MDMA-induced serotonergic neurotoxicity in various regions of rat brain.
Methods Tryptophan hydroxylase immunofluorescent staining was performed in vitro to observe the neural morphology in the serotonergic neurons derived from E15 embryonic rat brain. In the in vivo studies, male Sprague-Dawley rats were co-treated MDMA (10mg/kg, s.c.) with 3-MA (15mg/kg, i.p.) twice a day for 4 consecutive days. Small animal-PET coupled with 4-[18F]-ADAM was performed 2 weeks later and the specific uptake ratios (SURs) of 4-[18F]-ADAM were evaluated in the various brain regions of rats. In addition, the forced swimming test was also performed to investigate the depression-like behaviors in these rats.
Results The immunofluorescent studies show that the 3-MA reversed the neurodegeneration of serotonergic neurites induced by MDMA. In the PET imaging studies, the SURs data of 4-[18F]-ADAM demonstrate that MDMA could cause the decreased uptake of 4-[18F]-ADAM in various brain regions, such as midbrain, thalamus, hypothalamus, striatum and cortex of rats. When the rats were co-treated MDMA with 3-MA, the SURs decrement is less than those of MDMA-treated alone group. Furthermore, 3-MA treatment could decreased immobility time in forced swimming tests.
Conclusions These results suggest that 3-MA may provide a neuroprotective effect against MDMA-induced loss of SERT in rat brain.