Effects of neonatal alcohol dose and exposure window on long delay and trace eyeblink conditioning in juvenile rats.
Effects of neonatal alcohol dose and exposure window on long delay and trace eyeblink conditioning in juvenile rats.
复制标题
新生酒精剂量和暴露窗口对幼年大鼠长延迟和微量眨眼调节的影响。
DOI：
10.1016/j.bbr.2012.08.025
复制
发表时间：
2013
影响因子：
2.7
通讯作者：
Stanton,MarkE
中科院分区：
文献类型：
--
作者：
Murawski,NathenJ;Jablonski,SarahA;Brown,KevinL;Stanton,MarkE
在胎儿酒精谱系障碍(FASD)的人类和动物模型研究中，经典的眨眼条件作用已被用于评估学习和记忆损害。孕期暴露在人类和类似的大鼠身上会严重损害各种眨眼条件下的任务，但这些影响是如何受到变量的影响的，比如酒精暴露的时间和剂量，我们知之甚少。在一系列四个实验中，我们系统地研究了不同的酒精暴露时间和剂量如何影响幼年大鼠的长时间延迟和痕迹眨眼条件作用，这些任务都依赖于脑干-小脑回路，但不同的是，痕迹条件作用还会招募海马体和前额叶皮质。在一个“相当于妊娠晚期”的酒精暴露模型中，大鼠在出生后4-9天或7-9天暴露于两个酒精剂量之一的高剂量酒精暴露，这两个暴露窗口被认为是不同的小脑和海马区。以假插管和未处理大鼠为对照。作为青少年，来自每种处理条件的大鼠都接受了长时间延迟或痕迹眨眼条件反射任务的训练。在长时间延迟条件反射过程中，酒精暴露大鼠表现出与对照组相比的一般条件性损伤，高酒精剂量(5.25g/kg/天)暴露的大鼠比接受低剂量酒精(4.66g/kg/天)的大鼠损伤更严重。与对照组相比，酒精暴露的大鼠只有在PD 4-9或PD 7-9以上给予高剂量酒精时，才会出现痕迹条件反射障碍。这些发现表明，新生儿在PD 4-9和PD 7-9酒精暴露后，学习和记忆都会受到严重损害。延迟和痕迹条件反射的损害模式表明，酒精扰乱了这两项任务共同的过程。这些发现与FASD儿童的延迟和痕迹眨眼条件作用研究是一致的。未来对这些缺陷的机制的研究将进一步加深我们对发育期酒精暴露造成的脑损伤和记忆障碍的理解。
Classical eyeblink conditioning has been used to assess learning and memory impairments in both humans and animal model studies of fetal alcohol spectrum disorders (FASD). Gestational exposure to alcohol in humans and its equivalent in rats severely impairs various eyeblink conditioning tasks, but less is known about how these effects are influenced by variables, such as the timing and dose of alcohol exposure. In a series of four experiments, we systematically examine how varying the timing and dose of alcohol exposure impact long delay and trace eyeblink conditioning in juvenile rats, tasks that both depend on a brainstem-cerebellar circuit but differ in that trace conditioning additionally recruits the hippocampus and prefrontal cortex. Using a “third-trimester-equivalent” alcohol exposure model, rats were exposed to a high binge dose of alcohol at one of two alcohol doses over postnatal days (PD) 4–9 or PD 7–9, windows of exposure thought to differentially target the cerebellum and hippocampus. Sham-intubated and untreated rats served as controls. As juveniles, rats from each treatment condition were trained in either a long delay or trace eyeblink conditioning task. Alcohol-exposed rats demonstrated general conditioning impairments compared to controls during long delay conditioning, with more robust impairments in rats exposed to the higher alcohol dose (5.25g/kg/day) than those that received the lower dose (4.66g/kg/day). Alcohol-exposed rats showed trace conditioning impairments compared to controls only when the high dose of alcohol was administered over PD 4–9 or PD 7–9. These findings indicate significant learning and memory impairments following neonatal alcohol exposure at both PD 4–9 and PD 7–9. The pattern of impairments across delay and trace conditioning suggest that alcohol disrupts processes that are common to both tasks. These findings are consistent with studies of delay and trace eyeblink conditioning in children with FASD. Future studies of the mechanisms underlying these deficits will further our understanding of brain injury and memory impairments resulting from developmental alcohol exposure.