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长期认知损伤由青春期慢性大麻素暴露在大鼠中诱导:品系比较。

Long-term cognitive impairments induced by chronic cannabinoid exposure during adolescence in rats: a strain comparison.

机构信息

Laboratoire de "Physiopathologie des maladies Psychiatriques", Centre de Psychiatrie et Neurosciences U894, INSERM, Paris, France.

出版信息

Psychopharmacology (Berl). 2013 Feb;225(4):781-90. doi: 10.1007/s00213-012-2865-z. Epub 2012 Sep 16.

Abstract

RATIONALE

During cerebral development, adolescence is a critical phase in which the endocannabinoid system plays an important role in regulating various neurotransmitters. Moreover, evidence from both human and animal studies suggests that chronic cannabinoid exposure during this vulnerable period can induce persistent brain and behavioural alterations.

OBJECTIVES

The aim of this study was to compare the long-term cognitive consequences of chronic adolescence cannabinoid exposure between Lister Hooded rats and Wistar rats.

METHODS

Rats of both strains were injected daily throughout their adolescent or adult periods with vehicle or with incremental doses of the synthetic cannabinoid CB1 receptor agonist CP55,940 (CP). Short-term and spatial working memories were assessed using the object recognition and object location, tasks respectively. For both tasks, the effect of a 30- or 120-min delay between the learning and the testing phase was investigated.

RESULTS

In the object recognition task, adolescent CP exposure impaired short-term memory after both delays in both strains. In contrast, in the object location task, adolescent CP exposure impaired spatial working memory in the Wistar rats after a 30-min delay, whereas the Lister Hooded rats exhibited a similar effect only after a 120-min delay. In these tests, no long-term deleterious effects were found following adult CP exposure in either strain.

CONCLUSIONS

Our results confirm that adolescence is a critical period for the deleterious effects of cannabinoids on cognition and that these deleterious effects on spatial working memory are more strain-dependent than the effects observed on short-term memory.

摘要

背景

在大脑发育过程中,青春期是一个关键阶段,内源性大麻素系统在此期间对于调节各种神经递质起着重要作用。此外,来自人类和动物研究的证据表明,在这个易受伤害的时期慢性摄入大麻素会导致大脑和行为的持续改变。

目的

本研究旨在比较慢性青春期大麻素暴露对利斯特褐毛鼠和 Wistar 大鼠的长期认知后果。

方法

两种品系的大鼠在青春期或成年期每天接受载体或递增剂量的合成大麻素 CB1 受体激动剂 CP55,940(CP)注射。使用物体识别和物体位置任务分别评估短期和空间工作记忆。对于这两个任务,研究了学习和测试阶段之间 30 分钟或 120 分钟的延迟对其的影响。

结果

在物体识别任务中,青春期 CP 暴露在两种品系中均在 30 分钟和 120 分钟的延迟后损害了短期记忆。相比之下,在物体位置任务中,青春期 CP 暴露在 Wistar 大鼠中损害了空间工作记忆,而利斯特褐毛鼠仅在 120 分钟的延迟后出现类似的影响。在这些测试中,成年 CP 暴露在两种品系中均未发现长期的有害影响。

结论

我们的结果证实青春期是大麻素对认知产生有害影响的关键时期,并且这些对空间工作记忆的有害影响比观察到的短期记忆的影响更依赖于品系。

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