Durable changes in cognition and astrocytic bioenergetics after drug experience

 描述（由申请人提供）：暴露于滥用药物会改变神经元功能，表现为神经元生物学改变和行为改变。其中一些变化的持续时间比药物暴露时间长。同时，也有相当多的证据表明，暴露于滥用药物改变胶质星形胶质细胞的形态和功能。 星形胶质细胞糖原在大脑中作为能量储备，其降解在神经元激活期间开始。糖原按需代谢为乳酸，然后转运到神经元中作为能量底物。最近的研究表明，星形胶质细胞对神经元能量代谢的贡献是记忆和神经可塑性的关键调节因子。然而，星形胶质细胞形式和功能的变化与暴露于滥用药物后认知功能的改变没有直接联系。 我们最近发现，学习经验，在一个单一的1小时的训练课程，改变星形胶质细胞糖原储存和乳酸生产30天后在大鼠中，这些变化与任务和大脑区域。该项目将这些发现扩展到测试可卡因和吗啡治疗对糖原水平和乳酸产生变化的影响，直至药物暴露后30天，以及在以后的学习中星形胶质细胞活性的功能测量。基于先前确定的认知变化，不同的吗啡和可卡因暴露后，多个记忆系统的方法在这里使用纹状体和海马的神经化学措施，以及训练的任务，差异从事这些脑区。该项目将测试可卡因和吗啡暴露导致星形胶质细胞对大脑能量代谢的贡献发生长期变化的假设，并对药物经验对认知功能的持久影响产生重要影响。这些实验的发现可能是未来研究药物经历后认知和大脑长期变化的本质的基础。星形胶质细胞对药物暴露后生物能量学改变的贡献，以及学习和记忆能力的改变，可能为理解和改善药物暴露对大脑和行为的长期影响开辟新的途径。

 DESCRIPTION (provided by applicant): Exposure to drugs of abuse alter neuronal functioning, evident as both altered biology of the neurons and altered behaviors. Some of these changes long outlast the drug exposure. In parallel, there is also considerable evidence that exposure to drugs of abuse alters glial astrocyte morphology and function. Astrocytic glycogen serves as an energy reserve in the brain and its degradation is initiated during neuronal activation. Glycogen is metabolized on demand to lactate, which is then transported into neurons to serve as an energy substrate. Recent findings indicate that the contribution of astrocytes to energy metabolism in neurons is a key regulator of memory and neural plasticity. However, changes in astrocyte form and function have not been directly associated with the alteration in cognitive functions after exposure to drugs of abuse. We recently found that learning experiences, obtained during a single 1-hr training session, alter astrocytic glycogen storage and lactate production 30 days later in rats; these changes vary with task and brain area. This project extends these findings to test the effects of cocaine and morphine treatments on changes in glycogen levels and lactate production up to 30 days after drug exposure together with functional measures of astrocyte activity during later learning. Based on previously identified cognitive changes that differ after morphine and cocaine exposure, a multiple memory systems approach is applied here using neurochemical measures in striatum and hippocampus together with training on tasks that differentially engage these brain areas. This project will tes the hypotheses that cocaine and morphine exposure result in long-term changes in the contributions of astrocytes to brain energy metabolism with important consequences for enduring effects of drug experience on cognitive functions. The findings from these experiments may be foundational for future investigations into the nature of long-lasting changes in cognition and brain after drug experience. The contributions of astrocytes to altered bioenergetics after drug exposure, together with altered learning and memory abilities, may open new approaches to understanding and ameliorating the long-term consequences of drug exposures on brain and behavior.