Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY, USA.
Neuropsychopharmacology. 2018 Jan;43(1):21-33. doi: 10.1038/npp.2017.143. Epub 2017 Jul 7.
During adolescence, both rodent and human studies have revealed dynamic changes in the developmental trajectories of corticolimbic structures, which are known to contribute to the regulation of fear and anxiety-related behaviors. The endocannabinoid (eCB) system critically regulates stress responsivity and anxiety throughout the life span. Emerging evidence suggests that during adolescence, changes in eCB signaling contribute to the maturation of local and corticolimbic circuit populations of neurons, such as mediating the balance between excitatory and inhibitory neurotransmission within the prefrontal cortex. This function of the eCB system facilitates efficient communication within and between brain regions and serves a central role in establishing complex and adaptive cognitive and behavioral processing. Although these peri-adolescent changes in eCB signaling promote brain development and plasticity, they also render this period a particularly sensitive one for environmental perturbations to these normative fluctuations in eCB signaling, such as stress, potentially leading to altered developmental trajectories of neural circuits governing emotional behaviors. In this review, we focus on the role of eCB signaling on the regulation of stress and anxiety-related behaviors both during and after adolescence. Moreover, we discuss the functional implications of human genetic variation in the eCB system for the risk for anxiety and consequences of stress across development and into adulthood.
在青春期，啮齿动物和人类的研究都揭示了皮质边缘结构的发育轨迹发生了动态变化，这些结构被认为有助于调节恐惧和焦虑相关行为。内源性大麻素（eCB）系统在整个生命周期中对应激反应和焦虑起着关键的调节作用。新出现的证据表明，在青春期，eCB 信号的变化有助于神经元的局部和皮质边缘回路群体的成熟，例如介导前额叶皮层内兴奋性和抑制性神经传递之间的平衡。该 eCB 系统的这一功能促进了脑区内和脑区间的有效通讯，并在建立复杂和适应性认知和行为处理方面发挥着核心作用。尽管这些青春期前 eCB 信号的变化促进了大脑的发育和可塑性，但它们也使这一时期特别容易受到环境对 eCB 信号正常波动的干扰，例如压力，这可能导致控制情绪行为的神经回路的发育轨迹发生改变。在这篇综述中，我们重点讨论了 eCB 信号在调节青春期期间和之后的应激和焦虑相关行为中的作用。此外，我们还讨论了 eCB 系统中的人类遗传变异对整个发育过程和成年期焦虑风险和应激后果的功能意义。
