Early life is a critical period for the development of the central nervous system (CNS) when the brain undergoes functional organization, neuronal proliferation and migration. This study aimed to evaluate influences and possible interactions of the neonatal handling (NH) on morphologic, biochemical and molecular markers in the hippocampus, as well as on Mu opioid receptors (MOR) immunoreactivity when adolescent rats were exposed to morphine. On postnatal day (PND) 1, male pups were assigned to two experimental groups: unhandled (UH) or neonatal handling (NH), whose procedure was applied from PND2 to PND9. On PND 50, animals were submitted to memory behavioral test, anesthesia and euthanasia for blood collection and hippocampus removal. Animals exposed to NH showed: i) increased levels of proBDNF and brain-derived neurotrophic factor (BDNF); ii) increased memory performance; iii) decreased lipid peroxidation (LP) in plasma and hippocampus; iv) increased antioxidant defenses; v) increased glucocorticoids receptor (GR) levels. Interestingly, our data showed a positive correlation between BDNF and working memory after NH procedure (r² = 0.73; P = 0.006). Animals submitted to NH showed an increased per se of MOR immunoreactivity regardless of morphine exposure, while this increasing was also observed in the UH group after morphine exposure, even in a small extent. NH beneficial influence during early stage of life can be reflected during the development of the puppies, enhancing memory performance, preventing oxidative events and improving molecular targets in hippocampus. Further experimental studies in addition to clinical ones are needed to validate NH protocol as a therapeutic tool.

当大脑经历功能性组织、神经元增殖和迁移时，早期生命是中枢神经系统 (CNS) 发育的关键时期。本研究旨在评估新生儿处理 (NH) 对海马形态学、生化和分子标志物的影响和可能的相互作用，以及当青春期大鼠暴露于吗啡时对 Mu 阿片受体 (MOR) 免疫反应性的影响。在产后第 1 天 (PND)，雄性幼崽被分配到两个实验组：未处理 (UH) 或新生儿处理 (NH)，其程序从 PND2 到 PND9。在 PND 50 时，对动物进行记忆行为测试、麻醉和安乐死以进行血液采集和海马体去除。暴露于 NH 的动物显示：i) proBDNF 和脑源性神经营养因子 (BDNF) 的水平增加；ii) 提高内存性能；iii) 降低血浆和海马中的脂质过氧化 (LP)；iv) 增加抗氧化防御；v) 糖皮质激素受体 (GR) 水平增加。有趣的是，我们的数据显示 NH 程序后 BDNF 与工作记忆之间呈正相关（r²  = 0.73；P = 0.006）。无论是否接触吗啡，接受 NH 治疗的动物本身的 MOR 免疫反应性都会增加，而在接触吗啡后 UH 组中也观察到这种增加，即使程度很小。NH在生命早期的有益影响可以在幼犬的发育过程中反映出来，增强记忆性能，防止氧化事件和改善海马中的分子靶标。除了临床研究之外，还需要进一步的实验研究来验证 NH 协议作为一种治疗工具。