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产前和产后早期接触大麻与青少年慢性应激对焦虑样、抑郁样和冒险行为的相互作用。

Prenatal and early postnatal cannabis exposure interactions with adolescent chronic stress on anxiety-like, depression-like, and risk-taking behaviour.

作者信息

Peterson Colleen S, Ifionu Ijeoma, Hamood Fatima, Semizeh Hadi, Ali Ahmad, Noble Duncan, Qiao Min, Borgland Stephanie L

机构信息

Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

出版信息

Psychopharmacology (Berl). 2025 May 29. doi: 10.1007/s00213-025-06822-x.

Abstract

RATIONALE

Low socioeconomic status people make up a majority of those who use cannabis during pregnancy. Both developmental cannabis exposure and developmental stress increase the risk of developing psychiatric disorders; however, the interaction of these factors has not been studied.

OBJECTIVES

This study examined whether prenatal and early postnatal cannabis exposure (PPCE) impacted susceptibility to chronic adolescent stress in a dose- and environment-controlled animal model.

METHODS

Mouse dams orally consumed 5 mg/kg THC in whole cannabis oil daily from GD1-PD10. Offspring were exposed to chronic mild unpredictable stress throughout adolescence (PD28-56). From PD58, mice were challenged with a battery of tests to measure anxiety-like (elevated plus maze, open field test), stress coping (forced swim test, tail suspension test), anhedonia-like (sucrose preference), risk-taking behaviour (wire beam bridge), and social motivation (3 chamber sociability and social novelty task). Brain slices were taken 90 min after forced swim test to analyze c-Fos expression.

RESULTS

PPCE did not interact with chronic adolescent stress to impact anxiety-like, acute stress coping, or social motivation. However, co-exposed mice showed a significantly increased incidence of bridge crossing in the wire beam bridge task, whereas stress-only exposed animals did not. There were sex differences in c-FOS expression in the prefrontal cortex (PFC) in response to stress and PPCE.

CONCLUSIONS

These data indicate that PPCE, when combined with adolescent stress, increases risk-taking behaviour.

摘要

理论依据

社会经济地位低下的人群占孕期使用大麻者的大多数。孕期接触大麻和发育应激都会增加患精神疾病的风险;然而,这些因素之间的相互作用尚未得到研究。

目的

本研究在剂量和环境可控的动物模型中,考察产前和产后早期接触大麻(PPCE)是否会影响青少年对慢性应激的易感性。

方法

从妊娠第1天(GD1)至产后第10天(PD10),母鼠每天口服5mg/kg四氢大麻酚(THC)全大麻油。子代在整个青春期(PD28-56)接受慢性轻度不可预测应激。从PD58开始,对小鼠进行一系列测试,以测量类似焦虑的行为(高架十字迷宫、旷场试验)、应激应对能力(强迫游泳试验、悬尾试验)、类似快感缺失的行为(蔗糖偏好试验)、冒险行为(钢丝梁桥试验)和社交动机(三室社交和社交新奇性任务)。在强迫游泳试验90分钟后取脑片分析c-Fos表达。

结果

PPCE与青少年慢性应激之间不存在相互作用,不会影响类似焦虑的行为、急性应激应对能力或社交动机。然而,同时接触应激和大麻的小鼠在钢丝梁桥试验中的过桥次数显著增加,而仅接触应激的动物则没有。前额叶皮质(PFC)中c-FOS表达对应激和PPCE的反应存在性别差异。

结论

这些数据表明,PPCE与青少年应激相结合会增加冒险行为。

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