The lasting influence of social stressors in adolescence on development

发育的关键期或敏感期是指大脑正在经历快速生长并容易受到各种环境影响的时期。在这段时间里，压力和社会互动的质量等经历会对大脑功能产生相对永久性的影响。尽管许多研究表明产前和新生儿生活是发育的敏感时期，但青少年却很少受到研究人员的关注。我的实验室已经表明，青春期也是大脑持续发展的时期，受到压力源和社会互动的影响。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，在成年期实施的相同的社会不稳定程序没有与青春期相同的效果，这突出了应激源对动物个体发生阶段影响的重要性。有了这笔资金，我们建议研究青少年和成人在药物诱导可塑性方面差异的神经基础，以及压力对青少年发育中的大脑带来风险的方式。我们将使用免疫组织化学和western blot技术来检测与药物作用有关的神经区域的可塑性标记物。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，并使用自然奖励和药物相关奖励来研究中边缘系统功能。这项拟议的研究将增加对青春期作为大脑发育中性别特异性可塑性时期的理解，以及环境在塑造个体行为和大脑功能差异方面的作用。

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.