The lasting influence of social stressors in adolescence on development

发育的关键或敏感时期是大脑正在经历快速生长并容易受到各种环境影响的时期。 在这些时期，诸如暴露于压力和社会交往质量等经历可能会对大脑功能产生相对永久的影响。 虽然许多研究表明，产前和新生儿的生活是敏感的发展时期，青春期受到研究人员的关注较少。 我的实验室已经表明，青春期也是大脑持续发展的时期，这一时期受到压力源和社会互动的影响。我们迄今为止的研究表明，青春期的轻微社会压力会导致下丘脑-垂体-肾上腺功能的变化，增加焦虑样和抑郁行为的风险，并导致对滥用药物的行为反应的持久变化。重要的是，同样的社会不稳定的程序在成年期管理没有相同的影响，在青春期，这突出了个体发育阶段的动物的压力源的影响的重要性。 有了这笔赠款，我们建议调查青少年和成年人之间的差异，在药物诱导的可塑性和手段，压力赋予风险的发育中的大脑在青春期的神经基础。 我们将使用免疫组织化学和蛋白质印迹技术来检查与药物作用有关的神经区域的可塑性的几个标志物。 我们还将通过使用依赖于这些神经结构的行为措施来表征杏仁核和海马体的功能变化，并使用自然奖励和药物相关奖励来研究中脑边缘系统功能。这项拟议中的研究将增加对青春期的理解，青春期是大脑发育中性别特异性可塑性的时期，以及环境在塑造行为和大脑功能的个体差异方面的作用。

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.