Department of Pharmaceutical Biosciences, Division of Neuropharmacology, Addiction & Behavior, Uppsala University, Uppsala, Sweden.
Peptides. 2012 Jul;36(1):1-8. doi: 10.1016/j.peptides.2012.04.016. Epub 2012 Apr 27.
One major cause for discrepancies in results from animal experimental studies is the use of different animal strains and suppliers. We have previously reported that Wistar rats from five different suppliers display profound differences in ethanol intake and behavior. One of the neurobiological processes that could be underlying these differences is the endogenous opioid system, which has been implicated in the rewarding and reinforcing effects of alcohol. We therefore hypothesized that the differences between the supplier groups would also be evident in the endogenous opioid system. Radioimmunoassay was used to determine the levels of the opioid peptides Met-enkephalin-Arg(6)Phe(7) and dynorphin B in several brain areas of ethanol-drinking and ethanol naïve Wistar rats from five different suppliers. In the ethanol naïve animals, differences between the supplier groups were found in the pituitary gland, hypothalamus, frontal cortex, dorsal striatum and hippocampus. In the ethanol-drinking rats, differences were found in the same structures, with the addition of medial prefrontal cortex and substantia nigra. Correlations between ethanol intake and peptide levels were also found in several of the areas examined. The structures in which differences were found have all been implicated in the transition from drug use to addiction and these differences may lead to different propensities and vulnerability to this transition. Because the endogenous opioids have been suggested to be involved in a number of neurobiological disorders the results do not only have implications for research on alcohol or drug addiction, but many other fields as well.
导致动物实验研究结果差异的一个主要原因是使用不同的动物品系和供应商。我们之前曾报道过,来自五个不同供应商的 Wistar 大鼠在乙醇摄入量和行为方面存在显著差异。这些差异背后的一个神经生物学过程可能是内源性阿片系统,该系统已被牵涉到酒精的奖赏和强化作用中。因此,我们假设供应商群体之间的差异也会在内源性阿片系统中表现出来。放射免疫测定法用于测定来自五个不同供应商的饮酒和未饮酒的 Wistar 大鼠的几种脑区中的阿片肽 Met-enkephalin-Arg(6)Phe(7)和 dynorphin B 的水平。在未饮酒的动物中,在垂体、下丘脑、额叶皮质、背侧纹状体和海马体中发现了供应商群体之间的差异。在饮酒的大鼠中,在相同的结构中发现了差异,增加了内侧前额叶皮质和黑质。在几个检查的区域中还发现了乙醇摄入量和肽水平之间的相关性。发现差异的结构都与从药物使用到成瘾的转变有关,这些差异可能导致对这种转变的不同倾向和脆弱性。由于内源性阿片类物质被认为参与了许多神经生物学疾病,因此这些结果不仅对酒精或药物成瘾的研究具有意义,而且对许多其他领域也具有意义。