The lasting influence of social stressors in adolescence on development

大脑发育的关键或敏感期是大脑快速生长的时期，容易受到各种环境的影响。在这些时期，暴露在压力和社会互动质量中的经历可能会对大脑功能产生相对持久的影响。尽管许多研究表明，产前和新生儿是发育的敏感期，但青春期受到研究人员的关注较少。我的实验室表明，青春期也是大脑不断发育的时期，大脑的发育受到压力和社会互动的影响。到目前为止，我们的研究表明，青春期轻微的社会压力会导致下丘脑-垂体-肾上腺功能的变化，增加焦虑和抑郁行为的风险，并导致对滥用药物的行为反应的持久变化。重要的是，成年时实施的同样的社会不稳定程序并没有产生与青春期相同的效果，这突显了动物个体发育阶段在应激源影响下的重要性。利用这笔资金，我们建议调查青少年和成年人在药物诱导的可塑性方面存在差异的神经基础，以及压力对青春期发育中的大脑造成风险的方式。我们将使用免疫组织化学和免疫印迹技术来检测与药物效应有关的神经区域的几个可塑性标记物。我们还将通过使用依赖于这些神经结构的行为测量来表征杏仁核和海马体的功能变化，并使用与药物相关的奖励之外的自然奖励来研究中脑边缘系统的功能。这项拟议的研究将增加人们对青春期作为大脑发育性别可塑性时期的理解，以及环境在塑造个体行为差异和大脑功能方面的作用。

Critical or sensitive periods of development are times in which the brain is undergoing a rapid rate of growth and is susceptible to a variety of environmental influences. Experiences such as exposure to stress and quality of social interactions during these periods can lead to relatively permanent effects on brain function. Although much research has shown prenatal and neonatal life to be sensitive periods of development, adolescence has received less attention by researchers. My lab has shown that adolescence is also be a time when ongoing development of the brain is shaped by stressors and social interactions. Our research to date has shown that mild social stress in adolescence leads to changes in hypothalamic-pituitary-adrenal function, increases risk for anxiety-like and depressive behaviour, and leads to lasting changes in behavioural responses to drugs of abuse. Importantly, the same social instability procedure administered in adulthood did not have the same effects as in adolescence, which highlights the significance of the ontogenetic stage of the animal in the effects of stressors. With this grant, we propose to investigate the neural basis for differences between adolescents and adults in drug-induced plasticity and the means by which stress confers risk on the developing brain in adolescence. We will use immunohistochemistry and western blot techniques to examine several markers of plasticity in neural regions implicated in drug effects. We also will characterize functional changes in the amygdala and hippocampus through the use of behavioural measures that rely on these neural structures, and to investigate mesolimbic system function using naturalistic reward in addition to drug-related reward. The proposed research will increase the understanding of adolescence as a time of sex-specific plasticity in brain development, and the role of environment in shaping individual differences in behaviour and brain function.