Department of Psychology , Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
Alcohol Clin Exp Res. 2013 Sep;37(9):1561-70. doi: 10.1111/acer.12122. Epub 2013 May 3.
Effective treatments for the behavioral and cognitive deficits in children with fetal alcohol spectrum disorders (FASD) are lacking, and translational approaches using animal models can help develop rational interventions. One such model, binge-like alcohol exposure in neonatal rats during the period of brain development comparable with that of the human third trimester, causes structural and functional damage to the cerebellum and disrupts cerebellar-dependent eyeblink classical conditioning. The eyeblink conditioning deficits first demonstrated in this rat model predicted the similar deficits subsequently demonstrated in children with FASD.
The current study extends this translational approach by testing the hypothesis that rehabilitation training involving 20 days of training on traversal of an obstacle course (complex motor learning) would ameliorate the deficits on classical conditioning of eyeblink responses produced by the neonatal alcohol exposure. We have previously shown that this training stimulates cerebellar synaptic plasticity and improves alcohol-induced deficits on motor coordination tasks.
The current studies found that rehabilitation training significantly attenuated alcohol-induced deficits in acquisition of eyeblink conditioning in females but not in males. These results are consistent with normalization of cerebellar-dependent learning, at least in alcohol-exposed females.
These findings extend previous studies in this model suggesting that rehabilitation of adolescents with FASD using training with complex motor learning tasks could be effective in ameliorating functional impairments associated with cerebellar damage. Eyeblink classical conditioning deficits are now well documented in children with FASD and could serve as an evaluation measure to continue to develop therapeutic interventions such as complex motor learning.
胎儿酒精谱系障碍（FASD）儿童的行为和认知缺陷缺乏有效治疗方法，使用动物模型的转化方法可以帮助开发合理的干预措施。一种这样的模型是在类似于人类第三个 trimester 的大脑发育期间对新生大鼠进行 binge-like 酒精暴露，导致小脑的结构和功能损伤，并破坏小脑依赖的眨眼经典条件反射。在这种大鼠模型中首次证明的眨眼条件反射缺陷预测了随后在 FASD 儿童中证明的类似缺陷。
本研究通过测试以下假设来扩展这种转化方法，即涉及穿越障碍课程（复杂运动学习）的 20 天训练的康复训练将改善由新生酒精暴露引起的眨眼反应经典条件反射的缺陷。我们之前已经表明，这种训练刺激小脑突触可塑性，并改善酒精引起的运动协调任务缺陷。
目前的研究发现，康复训练显著减轻了女性而非男性中酒精引起的眨眼条件反射获得缺陷。这些结果与小脑依赖学习的正常化一致，至少在酒精暴露的女性中是这样。
这些发现扩展了该模型中的先前研究，表明使用复杂运动学习任务对 FASD 青少年进行康复训练可能有效改善与小脑损伤相关的功能障碍。眨眼经典条件反射缺陷现在在 FASD 儿童中得到了很好的记录，可以作为评估措施，继续开发治疗干预措施，如复杂运动学习。
