A recent study from our laboratory demonstrated that binge methamphetamine induced hippocampal cell damage (i.e., impaired cell genesis) in rats when administered specifically during late adolescence (postnatal day, PND 54-57) and evaluated 24 h later (PND 58). The results also suggested a possible role for brain-derived neurotrophic factor (BDNF) regulating cell genesis and survival. This subsequent study evaluated whether these effects persisted in time as measured following prolonged withdrawal. Male Sprague-Dawley rats were treated (i.p.) with BrdU (2 × 50 mg/kg, 3 days, PND 48-50) followed by a binge paradigm (3 pulses/day, every 3 h, 4 days, PND 54-57) of methamphetamine (5 mg/kg, n = 14, M) or saline (0.9% NaCl, 1 ml/kg, n = 12, C). Following 34 days of forced withdrawal (PND 91), rats were killed 45 min after a challenge dose of saline (Sal: C-Sal, n = 6; M-Sal, n = 7) or methamphetamine (Meth: C-Meth, n = 6; M-Meth, n = 7). Neurogenesis markers (Ki-67: cell proliferation; NeuroD: early neuronal survival; BrdU: prolonged cell survival, 41–43 days old cells) were evaluated by immunohistochemistry while neuroplasticity markers (BDNF and Fos forms) were evaluated by Western blot. The main results showed that a history of methamphetamine administration (PND 54-57) induced enduring hippocampal cell damage (i.e., observed on PND 91) by decreasing cell survival (BrdU + cells) and mature-BDNF (m-BDNF) protein content, associated with neuronal survival, growth and differentiation. Interestingly, m-BDNF regulation paralleled hippocampal c-Fos protein content, indicating decreased neuronal activity, and thus reinforcing the persisting negative effects induced by methamphetamine in rat hippocampus following prolonged withdrawal.

我们实验室的最新研究表明，暴饮暴食的甲基苯丙胺在青春期后期（产后一天，PND 54-57）特别给药，并在24小时后进行评估（PND 58），可诱发大鼠海马细胞损伤（即，细胞起源受损）。结果还表明脑源性神经营养因子（BDNF）调节细胞发生和存活的可能作用。这项后续研究评估了长期停药后这些效果是否持续存在。雄性Sprague-Dawley大鼠先后用BrdU（2×50 mg / kg，3天，PND 48-50）（ip）暴饮暴食（3脉冲/天，每3小时，4天，PND 54-57）处理（ip）甲基苯丙胺（5 mg / kg，n = 14，M）或盐水（0.9％NaCl，1 ml / kg，n = 12，C）。经过34天的强制撤离（PND 91），挑战剂量的生理盐水（Sal：C-Sal，n = 6; M-Sal，n = 7）或甲基苯丙胺（Meth：C-Meth，n = 6; M-Meth，n = 7）攻击后45分钟处死大鼠）。通过免疫组织化学评估神经发生标记（Ki-67：细胞增殖； NeuroD：早期神经元存活； BrdU：延长的细胞存活，41–43天龄细胞），而通过Western blot评估神经可塑性标记（BDNF和Fos形式）。主要结果表明，服用甲基苯丙胺（PND 54-57）的历史通过降低细胞存活率（BrdU +细胞）和成熟的BDNF（m-BDNF）蛋白质含量诱导了持久的海马细胞损伤（即在PND 91上观察到），与神经元存活，生长和分化有关。有趣的是，m-BDNF调节与海马c-Fos蛋白含量平行，表明神经元活性降低，