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青少年甲苯暴露会导致小鼠产生持久的社交和认知缺陷:溶剂诱导精神病的动物模型。

Adolescent toluene exposure produces enduring social and cognitive deficits in mice: an animal model of solvent-induced psychosis.

机构信息

Institute of Pharmacology and Toxicology, Hualien, Taiwan.

出版信息

World J Biol Psychiatry. 2010 Sep;11(6):792-802. doi: 10.3109/15622970903406234.

Abstract

OBJECTIVES

Abuse of toluene-containing volatile solvents by adolescents is a significant public health problem. The present study characterized the long-term behavioural and neurochemical consequences of toluene exposure during adolescence.

METHODS

Male NMRI mice received one injection per day of either toluene (600 mg/kg) or corn oil during postnatal days (PN) 35-37 and (750 mg/kg) during PN38-39 and PN42-46. A variety of psychiatric disorder-relevant behavioural tests were examined at PN56-P84.

RESULTS

The toluene-exposed mice were significantly deficient in the social interaction test, nesting behaviour, social dominance tube test, and novel objective recognition test. However, toluene exposure did not affect locomotor activity and behavioural profiles in the forced swimming test, tail suspension test, emergence test and elevated plus maze. Neurochemically, the turnover rates of dopamine in the prefrontal cortex, striatum and nucleus accumbens were reduced in toluene-treated mice.

CONCLUSIONS

Adolescent toluene exposure leads to social deficits and cognitive impairment at adulthood as well as neurochemical dysfunction in mice, which correlate with the symptoms observed in patients suffering from solvent-induced psychosis. These findings highlight the need for understanding the effects of solvent abuse on the developing nervous system and reveal an animal model suitable for research into pathophysiology of neurological and psychiatric consequences of solvent abuse.

摘要

目的

青少年滥用含甲苯的挥发性溶剂是一个严重的公共卫生问题。本研究旨在描述青春期接触甲苯对长期行为和神经化学的影响。

方法

雄性 NMRI 小鼠在出生后第 35-37 天(PN)每天接受一次甲苯(600mg/kg)或玉米油注射,在第 38-39 天和第 42-46 天(PN)每天接受一次 750mg/kg 甲苯或玉米油注射。在 PN56-P84 期间,对多种与精神疾病相关的行为测试进行了检查。

结果

甲苯暴露组的小鼠在社交互动测试、筑巢行为、社会统治管测试和新物体识别测试中表现出明显的缺陷。然而,甲苯暴露并未影响强迫游泳测试、悬尾测试、出现测试和高架十字迷宫中的运动活动和行为特征。神经化学方面,甲苯处理组的前额叶皮质、纹状体和伏隔核中的多巴胺周转率降低。

结论

青春期接触甲苯会导致成年后出现社交缺陷和认知障碍,以及小鼠的神经化学功能障碍,这些与溶剂诱导精神病患者的症状相吻合。这些发现强调了理解溶剂滥用对发育中神经系统的影响的必要性,并揭示了适合研究溶剂滥用对神经和精神疾病后果的病理生理学的动物模型。

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