Kirstein C L, Philpot R M, Dark T
Department of Psychology, University of South Florida, Tampa 33620, USA.
Int J Neurosci. 1997 Jan;89(1-2):119-32. doi: 10.3109/00207459708988467.
The goal of basic research examining the deficits underlying fetal alcohol syndrome is to develop an animal model which allows investigation and assessment of the neural and cognitive impairments resulting from prenatal alcohol exposure. The following review focuses on animal models and their relationship to human deficits following prenatal alcohol exposure. In addition, this review examines a unique, well-established model system which may permit an increased understanding of the role of alcohol on the developing brain and cognitive behavior. Specifically, large metabolic, neurochemical, neuropharmacological, morphological and neurophysiological changes in young rats have been reported as a consequence of early olfactory preference conditioning, a form of learning that normally occurs during both human and rat development. This olfactory odor preference training paradigm can be used to assess changes in learning as well as the neural substrates underlying this learning. Olfactory preference training has been used to examine: 1) learning, as demonstrated by a behavioral preference for an odor previously paired with stimulation which mimics maternal care; 2) metabolism, by measuring 2-deoxyglucose uptake and distribution in response to the trained odor; 3) neurotransmitter levels, by using in vivo microdialysis, to examine changes in neurotransmitter levels in the olfactory bulb in response to a trained odor. Using in vivo microdialysis enables measurement of both baseline responsiveness of alcohol-exposed pups as well as learned responses at several different developmental ages. The established neural features of this olfactory model include an increase in behavioral preference for a trained odor, increases in 2-DG uptake in specific foci within the olfactory bulb in response to the odor, and increases in dopamine in response to olfactory preference training stimuli, as well as conditioned increases in norepinephrine following olfactory preference training. Using these known behavioral, metabolic and neurochemical indices in control pups allows identification of some of the neurotransmitter systems involved in deficits and the neurobiological basis for impairments induced by prenatal alcohol exposure.
研究胎儿酒精综合征潜在缺陷的基础研究目标是建立一种动物模型，以便对产前酒精暴露导致的神经和认知损伤进行调查和评估。以下综述聚焦于动物模型及其与产前酒精暴露后人类缺陷的关系。此外，本综述还研究了一个独特且成熟的模型系统，该系统可能有助于加深我们对酒精在发育中大脑和认知行为作用的理解。具体而言，有报道称，幼鼠早期嗅觉偏好条件反射（一种在人类和大鼠发育过程中正常发生的学习形式）会导致其出现大规模的代谢、神经化学、神经药理学、形态学和神经生理学变化。这种嗅觉气味偏好训练范式可用于评估学习变化以及这种学习背后的神经基质。嗅觉偏好训练已被用于研究：1）学习，表现为对先前与模拟母性关怀的刺激配对的气味产生行为偏好；2）代谢，通过测量对训练气味的反应中2-脱氧葡萄糖的摄取和分布来评估；3）神经递质水平变化，通过体内微透析来检测嗅球中神经递质水平对训练气味的反应。使用体内微透析能够测量酒精暴露幼崽的基线反应性以及在几个不同发育阶段的学习反应。该嗅觉模型已确定的神经特征包括对训练气味的行为偏好增加、嗅球内特定区域对气味反应时2-DG摄取增加、对嗅觉偏好训练刺激的多巴胺增加以及嗅觉偏好训练后去甲肾上腺素的条件性增加。利用对照幼崽中这些已知的行为、代谢和神经化学指标，可以确定一些与缺陷相关的神经递质系统以及产前酒精暴露导致损伤的神经生物学基础。
