Gustafsson Lisa, Oreland Sadia, Hoffmann Pernilla, Nylander Ingrid
Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
Neuropeptides. 2008 Apr;42(2):177-91. doi: 10.1016/j.npep.2007.10.006. Epub 2007 Dec 20.
Early environmental influences can change the neuronal development and thereby affect behavior in adult life. The aim in the present study was to thoroughly examine the impact of early environmental factors on endogenous opioids by using a rodent maternal separation (MS) model. The endogenous opioid peptide system is not fully developed at birth, and short- and/or long-term alterations may occur in these neural networks in animals exposed to manipulation of the postnatal environment. Rat pups were subjected to one of five rearing conditions; 15 min (MS15) litter (l) or individual (i), 360 min (MS360) l or i daily MS, or housed under normal animal facility rearing (AFR) conditions during postnatal days 1-21. Measurements of immunoreactive (ir) Met-enkephalin-Arg6Phe7 (MEAP) and dynorphin B (DYNB) peptide levels in the pituitary gland and in a number of brain areas, were performed at three and 10 weeks of age, respectively. MS-induced changes were more pronounced in ir MEAP levels, especially in individually separated rats at three weeks of age and in litter-separated rats at 10 weeks of age. The enkephalin and dynorphin systems have different developmental patterns, dynorphin appearing earlier, which may point at a more sensitive enkephalin system during the early postnatal weeks. The results provide evidence that opioid peptides are sensitive for early environmental factors and show that the separation conditions are critical and also result in changes manifesting at different time points. MS-induced effects were observed in areas related to stress, drug reward and dependence mechanisms. By describing effects on opioid peptides, the study addresses the possible role of a deranged endogenous opioid system in the previously described behavioral consequences of MS.
早期环境影响可改变神经元发育,进而影响成年后的行为。本研究的目的是通过使用啮齿动物母婴分离(MS)模型,全面研究早期环境因素对内源性阿片类物质的影响。内源性阿片肽系统在出生时并未完全发育,在出生后环境受到操控的动物中,这些神经网络可能会发生短期和/或长期变化。将新生大鼠置于五种饲养条件之一;出生后第1 - 21天,每天进行15分钟(MS15)的窝养(l)或个体饲养(i)、360分钟(MS360)的窝养或个体饲养的母婴分离,或置于正常动物饲养设施(AFR)条件下饲养。分别在3周龄和10周龄时,测量垂体以及多个脑区中免疫反应性(ir)甲硫氨酸脑啡肽-精氨酸6 - 苯丙氨酸7(MEAP)和强啡肽B(DYNB)肽的水平。MS诱导的变化在ir MEAP水平上更为明显,尤其是在3周龄时个体分离的大鼠和10周龄时窝养分离的大鼠中。脑啡肽和强啡肽系统具有不同的发育模式,强啡肽出现得更早,这可能表明在出生后早期几周脑啡肽系统更敏感。结果提供了证据表明阿片肽对早期环境因素敏感,并表明分离条件至关重要,且还会导致在不同时间点出现变化。在与应激、药物奖赏和依赖机制相关的区域观察到了MS诱导的效应。通过描述对阿片肽的影响,本研究探讨了紊乱的内源性阿片系统在先前描述的MS行为后果中可能发挥的作用。