青少年大鼠的消退保持能力受损:D-环丝氨酸的影响。

Impaired extinction retention in adolescent rats: effects of D-cycloserine.

机构信息

University of New South Wales, Anzac Parade, Kensington, New South Wales, Australia.

出版信息

Neuropsychopharmacology. 2010 Sep;35(10):2134-42. doi: 10.1038/npp.2010.92. Epub 2010 Jun 30.

Abstract

The developmental trajectory of the prefrontal cortex (PFC) in both rats and humans is nonlinear, with a notable decline in synaptic density during adolescence, potentially creating a 'natural lesion' preparation at this age. Given that the PFC is critically involved in retention of extinction of learned fear in adult humans and rodents, the present study examined whether adolescent rats exhibit impaired extinction retention. The results of experiment 1 showed that adolescent rats were impaired in extinction retention, compared with both younger and older rats. The partial NMDA receptor agonist D-cycloserine (DCS) improved extinction retention in adolescent rats (experiment 2), but only if administered immediately after extinction training (experiment 3). In addition, providing extended extinction training improved extinction retention in adolescent rats in a manner similar to that of DCS (experiment 4). The results of this study show that adolescent rats exhibit impaired extinction retention, and that this can be reduced through either DCS or extended extinction training. These novel findings have potential implications for clinical treatments of fear and anxiety disorders in adolescent patients.

摘要

前额叶皮层(PFC)在大鼠和人类中的发展轨迹是非线性的,在青春期期间突触密度明显下降,可能在这个年龄段产生“自然损伤”。鉴于 PFC 在成年人类和啮齿动物中对习得性恐惧的消退的保留至关重要,本研究检查了青春期大鼠是否表现出消退保留受损。实验 1 的结果表明,与年轻和年长的大鼠相比,青春期大鼠在消退保留方面存在障碍。部分 NMDA 受体激动剂 D-环丝氨酸(DCS)可改善青春期大鼠的消退保留(实验 2),但仅在消退训练后立即给予时(实验 3)。此外,提供延长的消退训练以类似于 DCS 的方式改善了青春期大鼠的消退保留(实验 4)。这项研究的结果表明,青春期大鼠表现出消退保留受损,而这可以通过 DCS 或延长的消退训练来减少。这些新发现可能对青少年患者的恐惧和焦虑障碍的临床治疗具有重要意义。

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