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青少年期条件性恐惧消退的免疫组化分析。

Immunohistochemical analyses of long-term extinction of conditioned fear in adolescent rats.

机构信息

School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.

出版信息

Cereb Cortex. 2011 Mar;21(3):530-8. doi: 10.1093/cercor/bhq116. Epub 2010 Jun 24.

Abstract

Adolescence is a period of heightened emotional reactivity and vulnerability to poor outcomes (e.g., suicide, anxiety, and depression). Recent human and animal neuroimaging studies suggest that dramatic changes in prefrontal cortical areas during adolescence are involved in these effects. The present study explored the functional implications of prefrontal cortical changes during adolescence by examining conditioned fear extinction in adolescent rats. Experiment 1 showed that preadolescent (i.e., postnatal day [P] 24), adolescent (P35), and adult (P70) rats express identical extinction acquisition following 3 white-noise conditioned stimulus (CS) and shock pairings. When tested the next day, however, adolescent rats showed almost complete failure to maintain extinction of CS-elicited freezing compared with P24 and P70 rats. It was observed in experiment 2 that following extinction, P24 and P70 rats express significantly elevated levels of phosphorylated mitogen-activated protein kinase (pMAPK) in the infralimbic cortex (IL) compared with adolescent rats. Interestingly, adolescent rats successfully exhibited long-term extinction if the amount of extinction training was doubled (experiment 3). More extinction training also led to increased phosphorylation of MAPK in the IL in these rats. These findings suggest that adolescents are less efficient in utilizing prefrontal areas, which may lead to an impairment in the maintenance of extinguished behavior.

摘要

青春期是情绪反应强烈和容易出现不良后果(如自杀、焦虑和抑郁)的时期。最近的人类和动物神经影像学研究表明,青春期前额皮质区域的剧烈变化与这些影响有关。本研究通过检查青春期大鼠的条件性恐惧消退来探讨前额皮质变化的功能意义。实验 1 表明,幼年(即出生后第 24 天)、青春期(P35)和成年(P70)大鼠在接受 3 次白噪声条件刺激(CS)和电击配对后,表现出相同的消退获得。然而,第二天测试时,与 P24 和 P70 大鼠相比,青春期大鼠几乎完全未能维持 CS 诱发的冻结的消退。实验 2 观察到,与 P24 和 P70 大鼠相比,青春期大鼠在眶额皮层(IL)中表达的磷酸化丝裂原活化蛋白激酶(pMAPK)水平显著升高。有趣的是,如果增加消退训练的次数(实验 3),青春期大鼠也能成功表现出长期的消退。在这些大鼠中,更多的消退训练也导致了 IL 中 MAPK 的磷酸化增加。这些发现表明,青少年在利用前额皮质区域方面效率较低,这可能导致消退行为的维持受损。

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