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首页> 外文期刊>Journal of applied toxicology >Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic recept
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Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic recept

机译：对直接给药和母体分离引起的新生小鼠神经化学终点上潜在体温混杂因素的关键分析：对脑中毒蕈碱受体的生物Allethrin和溴氰菊酯与温度相互作用的研究

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The present investigation was conducted to understand better possible confounding factors caused by direct dosing of neonatal mice during the pre-weaning developmental period. By direct dosing, pups might encounter thermal challenges when temporarily removed from their 'natural habitat'. Typically, this leads to a cold environment and food deprivation (impaired lactation) and modulation of the toxic potency of the substance administered. Growth retardation as a consequence of such behavioural changes in pups makes it increasingly difficult to differentiate specific from non-specific mechanisms. Neonatal NMRI mice were dosed daily by gavage (0.7 mg kg(-1) body wt.) from postnatal day (PND) 10-16 with S-bioallethrin, deltamethrin or the vehicle. Then the pups, including their non-treated foster dams, were subjected temporarily for 6 h day to a hypo-, normo- or hyperthermic environment, which was followed by normal housing. The measured temperatures in the environmental chambers were ca. 21, 25 and 30 degrees C, respectively. Thus, temperatures in the hypo- and normothermic groups are comparable to the temperatures commonly present in testing laboratories, whereas the hyperthermic condition is that temperature typically present in the 'natural habitat' of pups. A deviation from the normal behaviour of both pups and dams was observed in the hypo- and normothermic groups. In these groups the rectal temperatures of pups were markedly decreased, especially in the early phase of the study (PND 10-12). Neonates that received either test substance displayed changes in body weights and brain weights at terminal sacrifice (PND 17) when subjected temporarily to a non-physiological environment. An enormous influence of environmental temperature on the density of muscarinic receptors in the crude synaptosomal fraction of the cerebral cortex was ascertained. In summary, these results demonstrate that the direct dosing of thermolabile neonatal mice by gavage is subject to significant artefacts that render the interpretation of findings from such studies difficult. It appears that if direct dosing of neonatal pups is mandated, and inhalation is a relevant route of exposure, the combined inhalation exposure of dams with their litters is an alternative procedure that does not cause disruption of the 'natural habitat' of pups. However, owing to their higher ventilation, under such conditions the pups may receive dosages at least double those of the dams.
机译：进行本研究的目的是为了更好地理解由断奶前发育期间直接给药新生小鼠引起的混杂因素。通过直接给药，幼仔暂时从其“自然栖息地”中移出时可能会遇到热挑战。通常，这导致寒冷的环境和食物匮乏（泌乳能力减退）以及所用物质毒性毒性的调节。由于幼崽的这种行为变化而导致的发育迟缓使得区分特异机制和非特异机制变得越来越困难。新生NMRI小鼠每天从产后第10-16天（PND）灌胃（0.7 mg kg（-1）体重），并用S-生物Allethethrin，溴氰菊酯或赋形剂给药。然后，将幼崽（包括未经处理的寄居水坝）暂时置于低温，常温或高温环境中放置6小时，然后进行正常饲养。在环境室中测得的温度约为分别为21、25和30摄氏度。因此，低温和常温组的温度与测试实验室中通常存在的温度相当，而高温条件是幼犬“自然栖息地”中通常存在的温度。在低体温和正常体温组中观察到与幼犬和大坝正常行为的偏差。在这些组中，幼崽的直肠温度明显降低，尤其是在研究的早期阶段（PND 10-12）。当暂时处于非生理环境时，接受这两种测试物质的新生儿在最终牺牲时（PND 17）显示出体重和脑重量的变化。确定了环境温度对大脑皮层的粗突触体部分中毒蕈碱受体密度的巨大影响。总而言之，这些结果表明，通过管饲法直接给不耐热的新生小鼠给药有明显的伪像，这使得对此类研究结果的解释变得困难。看来，如果强制要求直接给新生幼崽服药，并且吸入是相关的接触途径，则将大坝及其垫料联合吸入是不影响幼崽“自然栖息地”的替代方法。但是，由于它们较高的通风，在这种情况下，幼犬的剂量至少是大坝的两倍。

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