Several studies have identified the effects of methamphetamine (MA) on central dopaminergic neurons, but its effects on enteric dopaminergic neurons (EDNs) are unclear. The aim of this study was to investigate the effects of MA on EDNs and intestinal motility. Male Sprague–Dawley rats were randomly divided into MA group and saline group. The MA group received the multiple high-dose MA treatment paradigm, while the controls received the same saline treatment. After enteric motility was assessed, different intestinal segments (i.e., duodenum, jejunum, ileum, and colon) were taken for histopathological, molecular biological, and immunological analysis. The EDNs were assessed by measuring the expression of two dopaminergic neuronal markers, dopamine transporter (DAT) and tyrosine hydroxylase (TH), at the transcriptional and protein levels. We also used c-Fos protein, a marker of neural activity, to detect the activation of EDNs. MA resulted in a significant reduction in TH and DAT mRNA expression as well as in the number of EDNs in the duodenum and jejunum (p < 0.05). MA caused a dramatic increase in c-Fos expression of EDNs in the ileum (p < 0.001). The positional variability of MA effects on EDNs paralleled the positional variability of its effect on intestinal motility, as evidenced by the marked inhibitory effect of MA on small intestinal motility (p < 0.0001). This study found significant effects of MA on EDNs with locational variability, which might be relevant to locational variability in the potential effects of MA on intestinal functions, such as motility.

几项研究已经确定了甲基苯丙胺（MA）对中枢多巴胺能神经元的影响，但其对肠多巴胺能神经元（EDN）的影响尚不清楚。本研究的目的是研究 MA 对 EDN 和肠道蠕动的影响。雄性Sprague-Dawley大鼠随机分为MA组和生理盐水组。MA组接受多次高剂量MA治疗模式，而对照组接受相同的盐水治疗。评估肠蠕动后，取不同的肠段（即十二指肠、空肠、回肠和结肠）进行组织病理学、分子生物学和免疫学分析。通过测量两种多巴胺能神经元标记物——多巴胺转运蛋白（DAT）和酪氨酸羟化酶（TH）在转录和蛋白质水平上的表达来评估 EDN。我们还使用 c-Fos 蛋白（神经活动标记）来检测 EDN 的激活。MA 导致十二指肠和空肠中 TH 和 DAT mRNA 表达以及 EDN 数量显着减少 ( p  < 0.05)。MA 导致回肠中 EDN 的 c-Fos 表达显着增加 ( p  < 0.001)。MA 对 EDN 影响的位置变异性与其对肠蠕动影响的位置变异性平行，MA 对小肠蠕动的显着抑制作用证明了这一点 ( p  < 0.0001)。这项研究发现，MA 对 EDN 的显着影响具有位置变异性，这可能与 MA 对肠道功能（如蠕动性）的潜在影响的位置变异性有关。