Abstract
Methamphetamine (METH) is a highly neurotoxic psychoactive substance that can directly damage the central nervous system through prolonged use. Oxytocin (OT) has attracted much attention because of its neuroprotective effect. The purpose of this study was to investigate whether OT is neuroprotective against METH-induced damage in rat hippocampal neurons. Our results revealed that pre-incubation with OT significantly prevented the damage of METH to hippocampal neurons, including the decrease of mitochondrial membrane potential and the increase of ROS (reactive oxygen species). OT pre-incubation attenuated the up-regulation of Cleaved-Caspase-3 expression and the down-regulation of Bcl-2/Bax expression induced by METH. Pre-incubation with OT prevented the decrease in oxytocin receptor density and P-CREB (phosphorylation of cAMP-response element binding) expression induced by METH in rat hippocampal neurons. Moreover, Pre-incubation of atosiban (ATO) significantly prevented these changes. In conclusion, our study proved that pre-administration of OT could significantly attenuate hippocampal neuron apoptosis induced by METH. Oxytocin receptor activation is involved in the preventive effect of OT on METH-induced apoptosis in rat hippocampal neurons.
Highlights
The expanding abuse of METH has become a serious public crisis because of its strong addictiveness
4 mM METH significantly reduced the viability of hippocampal neurons, which are similar to METH concentration reported in FIGURE 2 | measures reactive oxygen species (ROS) production. (×20 objective; Scale bar 50 μm). (E,G) Cells were observed by confocal microscope after stained with the Fluorescent dye JC-1, JC-1 polymer/JC-I monomer measures the level of mitochondrial membrane potential. (×20 objective; Scale bar 50 μm)
Studies have demonstrated that OT has inhibitory effects against METHinduced conditioned place preference (CPP) and the recurrence of CPP caused by restraint stress, which could be prevented by ATO (Qi et al, 2009)
Summary
The expanding abuse of METH has become a serious public crisis because of its strong addictiveness. Excessive overuse of METH will cause various mental symptoms and be harmful to the central nervous system. METH is a cationic lipophilic molecule that enters and stores in mitochondria, reduces mitochondrial membrane potential and interferes with the mitochondrial biosynthesis, such as ATP synthesis, resulting in increased levels of reactive oxygen species (ROS), leading to apoptosis (Lemasters et al, 1999; Wu et al, 2007). METH has been shown to cause cell death through dopa-mediated and glutamate-mediated pathways: After METH enters the dopaminergic matrix, it will promote the oxidation of dopamine to superoxide, and superoxide and nitric oxide react to form peroxynitrite, which leads to cell death; Dopamine can promote the release of glutamate to activate NMDA receptor, resulting in increased production of nitric oxide and activation of the caspase cascade (Davidson et al, 2001).
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