Gondré-Lewis Marjorie C, Darius Philippe J, Wang Hong, Allard Joanne S
Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, United States; Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, United States.
Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, United States; Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, United States.
J Chem Neuroanat. 2016 Oct;76(Pt B):122-132. doi: 10.1016/j.jchemneu.2016.02.004. Epub 2016 Mar 2.
The experience of early life stress can trigger complex neurochemical cascades that influence emotional and addictive behaviors later in life in both adolescents and adults. Recent evidence suggests that excessive alcohol drinking and drug-seeking behavior, in general, are co-morbid with depressive-like behavior. Both behaviors are reported in humans exposed to early life adversity, and are prominent features recapitulated in animal models of early life stress (ELS) exposure. Currently, little is known about whether or how ELS modulates reward system nuclei. In this study we use operant conditioning of rats to show that the maternal separation stress (MS) model of ELS consumes up to 3-fold greater quantities of 10% vol/vol EtOH in 1-h, consistently over a 3-week period. This was correlated with a significant 22% reduction in the number of dopaminergic-like neurons in the VTA of naïve MS rats, similar to genetically alcohol-preferring (P) rats which show a 35% reduction in tyrosine hydroxylase (TH)-positive dopaminergic neurons in the VTA. MS rats had a significantly higher 2-fold immobility time in the forced swim test (FST) and reduced sucrose drinking compared to controls, indicative of depressive-like symptomology and anhedonia. Consistent with this finding, stereological analysis revealed that amygdala neurons were 25% greater in number at P70 following MS exposure. Our previous examination of the dentate gyrus of hippocampus, a region involved in encoding emotional memory, revealed fewer dentate gyrus neurons after MS, but we now report this reduction in neurons occurs without effect on the number of astrocytes or length of astrocytic fibers. These data indicate that MS animals exhibit neuroanatomical changes in reward centers similar to those reported for high alcohol drinking rats, but aspects of astrocyte morphometry remained unchanged. These data are of high relevance to understand the breadth of neuronal pathology that ensues in reward loci following ELS.
早年生活应激的经历可引发复杂的神经化学级联反应，影响青少年和成年人日后的情绪及成瘾行为。最近的证据表明，一般而言，过度饮酒和觅药行为与类似抑郁的行为共病。在经历早年生活逆境的人类中均有这两种行为的报道，并且在早年生活应激（ELS）暴露的动物模型中也再现了这些突出特征。目前，关于ELS是否以及如何调节奖赏系统核团知之甚少。在本研究中，我们利用大鼠的操作性条件反射表明，ELS的母性分离应激（MS）模型在3周的时间内，1小时内消耗的10%（体积/体积）乙醇量高达对照组的3倍。这与未接触过MS的幼稚大鼠腹侧被盖区（VTA）中多巴胺能样神经元数量显著减少22%相关，类似于遗传性嗜酒（P）大鼠，后者VTA中酪氨酸羟化酶（TH）阳性多巴胺能神经元减少35%。与对照组相比，MS大鼠在强迫游泳试验（FST）中的不动时间显著增加2倍，蔗糖摄取减少，表明存在类似抑郁的症状和快感缺失。与此发现一致，立体定位分析显示，MS暴露后70日龄时杏仁核神经元数量增加25%。我们之前对海马齿状回（一个参与编码情绪记忆的区域）的检查发现，MS后齿状回神经元数量减少，但我们现在报告这种神经元数量的减少并未影响星形胶质细胞的数量或星形胶质纤维的长度。这些数据表明，MS动物在奖赏中枢表现出与高饮酒大鼠报道的类似的神经解剖学变化，但星形胶质细胞形态学的某些方面保持不变。这些数据对于理解ELS后奖赏位点出现的神经元病理学广度具有高度相关性。
