In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact diverse social and cognitive abilities. This stage in development partially overlaps with the third human gestational trimester, commonly referred to as the brain growth spurt period. At this stage in development, human fetuses and rat neonates (postnatal days [PD] 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism, given that there are explicit associations between exteroceptive stimuli and the state of ethanol intoxication. Furthermore, studies performed with near-term rat fetuses suggest heightened sensitivity to ethanol's motivational effects. The present study was meant to analyze the unconditioned effects of ethanol intoxication and the possible co-occurrence of learning mechanisms that can impact respiratory plasticity, and to analyze the preference for cues that signal the state of intoxication as well as the effects of the drug, related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not paired with the effects of vehicle or ethanol (2.0 g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7, and 9 allowed the identification of the emergence of ethanol-derived non-associative and associative learning processes that affect breathing plasticity, particularly when considering apneic disruptions. Ethanol was found to partially inhibit the disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug's effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and ethanol intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor-stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables, it appears that most ethanol-derived changes are modulated by positive and/or negative (anti-anxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of ethanol-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal ethanol's motivational effects. These results emphasize the need to consider significant alterations due to minimal ethanol experiences that argue against "safe" levels of exposure in a critical stage in brain development.

中文翻译：

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基于触觉辨别程序的新生大鼠乙醇相关的呼吸和动机学习过程的共存。

在大鼠中，产后早期的高剂量乙醇会对大脑发育产生有害影响，从而影响多种社交和认知能力。发育的这个阶段与人类妊娠的第三孕期部分重叠，通常被称为大脑生长突增期。在发育的这个阶段，人类胎儿和大鼠新生儿（出生后[PD] 3-9天）表现出较高的呼吸频率，受致畸菌性乙醇剂量的影响。最近的研究表明，在发展中的生物体中，条件上的呼吸反应是有条件的，因为在这种情况下，外泌性刺激与乙醇中毒状态之间存在明显的联系。此外，对近期大鼠胎儿进行的研究表明，对乙醇激励作用的敏感性增强。本研究旨在分析乙醇中毒的无条件影响以及可能影响呼吸可塑性的学习机制的可能同时发生，并分析对表明中毒状态以及药物作用的线索的偏好，与运动刺激有关。新生大鼠经历了明显的触觉提示与载体或乙醇（2.0 g / kg）的影响配对或不配对的差异体验。PD 3，PD 5，PD 7，PD 9期间采用的触觉辨别程序可以识别出影响呼吸可塑性的乙醇来源的非联想和联想学习过程的出现，特别是考虑到呼吸暂停中断时。发现乙醇部分抑制了破坏，该破坏似乎与实验程序定义的压力环境密切相关。还观察到触觉提示与药物作用配对，对这些呼吸中断产生抑制作用。给定的触觉提示与乙醇中毒之间的偶然性水平也导致在触觉偏好测试中寻找该提示的可能性发生了重大变化。另外，中毒状态发挥运动刺激作用。当对比通过分析不同因变量获得的数据时，似乎大多数乙醇衍生的变化都受到药物的正和/或负（抗焦虑）增强作用的调节。整体而言 这项研究表明，在发展中的生物体中，与乙醇相关的功能性变化并存，同时会影响呼吸可塑性和信号刺激乙醇所激发的偏好模式。这些结果强调需要考虑由于乙醇经验最少而引起的重大改变，这与大脑发育关键阶段的“安全”暴露水平相抵触。