Impact of early developmental experience on cocaine-stress interactions in adulthood: An exploration of behavioural, physiological, and neural mechanisms

早期发展经验的影响可能是普遍和持久的，并可能影响与处理情绪，压力和奖励相关信息有关的基本神经和动机系统。由于这些系统以动态和复杂的方式相互作用和适应，因此了解它们的急性激活如何受到过去经验的影响是很重要的。从这个角度来看，有趣的是，母亲在怀孕前暴露于精神兴奋剂的影响可以传递给下一代，导致对影响的敏感性增强（例如，兴奋剂和焦虑样）的药物，如可卡因在成年后代。同样，在出生后早期暴露于压力（即，婴儿期）是大脑奖赏和压力相关系统发育的关键时期，可导致情绪以及对精神兴奋剂的行为和神经反应的长期变化。 拟议的研究计划将利用行为，生理和神经方法的组合来研究早期发育经验，包括怀孕前的母亲可卡因暴露和婴儿期的生活压力，如何改变成年后压力与可卡因之间的关系。虽然已知怀孕前暴露于精神刺激剂会改变成年后代的神经发育和行为，但尚不清楚这种经历对出生后早期神经发育的关键时期有什么影响。同样，尚不清楚母亲在怀孕前接触可卡因的影响是否会影响产后早期经历的生活压力的影响。然而，考虑到压力和奖励相关的回路如何密切地相互作用，以介导成年后压力源和精神兴奋剂的直接影响，以及它们对过去的经验有多敏感，这些都是重要的研究问题。目前的研究计划将解决这些问题，更普遍地说，将提供重要的洞察力，了解大脑如何对早期生活经验作出反应，这种反应可能会使人们对以后生活中经历的事件产生脆弱性。

The effects of early developmental experience can be pervasive and long lasting, and can impact on fundamental neural and motivational systems relating to the processing of emotional-, stress-, and reward-relevant information. Because these systems interact and adapt in a dynamic and complex way, it is important to understand how their acute activation is influenced by past experience. From this perspective, it is of interest that the effects of maternal exposure to psychostimulants before pregnancy can be transmitted to the next generation, resulting in enhanced sensitivity to the effects (e.g., stimulant and anxiety-like) of drugs like cocaine in adult offspring . Likewise, exposure to stress during the early postnatal period (i.e., infancy), a critical time for development of reward- and stress-related systems of the brain, can lead to long-term changes in emotionality, and in behavioural and neural responses to psychostimulants. The proposed program of research will utilize a combination of behavioural, physiological, and neural methods to examine how early developmental experience, including maternal cocaine exposure before pregnancy and life stress in infancy, serves to alter the relationship between stress and cocaine in adulthood. Although psychostimulant exposures before pregnancy are known to alter neural development and behaviour in adult offspring, it is not known what effect that experience has in the early postnatal period, a critical period of neural development. Likewise, it is not known whether the effects of maternal cocaine exposure before pregnancy influence the effect of life stress experienced during the early postnatal period. However, given how intimately stress- and reward-related circuitry are known to interact to mediate the direct effects of stressors and psychostimulants in adulthood, and how sensitive they are to past experience, these are important research questions. The present program of research will address these questions and, and more generally, will provide significant insight into how the brain responds to early life experience in a way that may confer vulnerability to events experienced later in life.