Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH‐induced dopamine neurotransmitter release, reactive oxygen species formation, and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH‐induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway. Four‐day‐old postnatal rats were subcutaneously injected with 5‐10 mg/kg AMPH and pretreated with 10 mg/kg melatonin prior to AMPH exposure for seven days. The results showed that melatonin decreased the AMPH‐induced hippocampal neuronal degeneration in the dentate gyrus, CA1, and CA3. Melatonin attenuated the reduction in the expression of hippocampal synaptophysin, PSD‐95, α‐synuclein, and N‐methyl‐D‐aspartate (NMDA) receptor protein and mRNA caused by AMPH. Melatonin attenuated the AMPH‐induced reduction in dopamine transporter (DAT) protein expression in the hippocampus and the reduction in mRNA expression in the ventral tegmental area (VTA). Immunofluorescence demonstrated that melatonin not only prevented the AMPH‐induced loss of DAT and NMDA receptor but also prevented AMPH‐induced α‐synuclein overexpression in the dentate gyrus, CA1, and CA3. Melatonin decreased the AMPH‐induced reduction in the protein and mRNA of the NMDA receptor downstream signaling molecule, calcium/calmodulin‐dependent protein kinase II (CaMKII), and the melatonin receptors (MT1 and MT2). This study showed that melatonin prevented AMPH‐induced toxicity in the hippocampus of postnatal rats possibly via its antioxidative effect and mitochondrial protection.

中文翻译：

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褪黑素对苯丙胺诱导的新生大鼠海马多巴胺能纤维变性的神经保护作用

慢性苯丙胺（AMPH）滥用会导致海马体受损，海马体是与学习和记忆过程相关的大脑区域。先前的结果表明，AMPH诱导的多巴胺神经递质释放，活性氧形成和变性蛋白质聚集会导致神经元死亡。褪黑激素，一种强大的抗氧化剂，起着神经保护剂的作用。这项研究的目的是研究褪黑激素对多巴胺能途径对产后大鼠AMPH诱导的海马损伤的保护作用。对四天大的产后大鼠皮下注射5-10 mg / kg的AMPH，并在AMPH暴露前7天对其进行10 mg / kg的褪黑素预处理。结果表明，褪黑素减少了齿状回，CA1和CA3中AMPH诱导的海马神经元变性。褪黑素可减轻由AMPH引起的海马突触素，PSD-95，α-突触核蛋白和N-甲基-D-天冬氨酸（NMDA）受体蛋白和mRNA的表达下降。褪黑素减弱了AMPH诱导的海马多巴胺转运蛋白（DAT）蛋白表达的减少和腹侧被盖区（VTA）mRNA表达的减少。免疫荧光表明褪黑素不仅可以防止AMPH诱导的DAT和NMDA受体丢失，而且还可以防止AMPH诱导的齿状回，CA1和CA3中α-突触核蛋白的过度表达。褪黑素降低了AMPH诱导的NMDA受体下游信号分子，钙/钙调蛋白依赖性蛋白激酶II（CaMKII）和褪黑素受体（MT1和MT2）的蛋白质和mRNA的减少。