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青春期大鼠慢性间歇性吸入甲苯后工具性学习的特定损伤。

Specific impairments in instrumental learning following chronic intermittent toluene inhalation in adolescent rats.

作者信息

Dick Alec L W, Axelsson Martin, Lawrence Andrew J, Duncan Jhodie R

机构信息

Florey Institute of Neuroscience and Mental Health, University of Melbourne, L3, Kenneth Myer Building, Cnr Genetics Lane on Royal Parade, Parkville, Melbourne, Victoria, 3010, Australia.

出版信息

Psychopharmacology (Berl). 2014 Apr;231(8):1531-42. doi: 10.1007/s00213-013-3363-7. Epub 2013 Dec 10.

Abstract

RATIONALE

Inhalant abuse is prevalent in adolescent populations, with chronic use resulting in neurobiological and cognitive abnormalities in adulthood. However, the nature and persistence of cognitive dysfunction, particularly following adolescent inhalant abuse, remain equivocal.

OBJECTIVE

The present study assessed specific cognitive processes beginning in late adolescence and adulthood following adolescent inhalation of toluene, a main component of many compounds readily abused.

METHODS

Adolescent male Wistar rats (postnatal day (PN) 27) were exposed to chronic intermittent inhaled toluene (10,000 ppm) for 1 h/day, 3 days/week for 4 weeks (PN 27-52) to mimic the patterns observed in human adolescent inhalant abusers. Following toluene exposure, motor and cognitive function was assessed.

RESULTS

Adolescent toluene exposure did not alter motor learning in the Rotarod task (PN 58) or acquisition, reversal, or retention of spatial learning in the Morris water maze (PN 55-64). In contrast, it delayed acquisition of instrumental responding for sucrose (5 % w/v) and impaired operant reversal learning and cue-induced reinstatement of sucrose seeking in adulthood (PN 57-100).

CONCLUSION

This study demonstrates that exposure to toluene at an abuse concentration during adolescence results in specific impairments in aspects of instrumental learning, without altering motor function and spatial learning in late adolescence/early adulthood. Our data imply that persistent alterations in reward processing may occur following adolescent inhalant misuse.

摘要

原理

吸入剂滥用在青少年群体中很普遍,长期使用会导致成年后出现神经生物学和认知异常。然而,认知功能障碍的性质和持续性,尤其是青少年吸入剂滥用后的情况,仍不明确。

目的

本研究评估了青少年吸入甲苯(许多易被滥用化合物的主要成分)后,从青春期晚期到成年期的特定认知过程。

方法

将青春期雄性Wistar大鼠(出生后第27天)暴露于慢性间歇性吸入甲苯(10,000 ppm)中,每天1小时,每周3天,持续4周(出生后第27 - 52天),以模拟人类青少年吸入剂滥用者的情况。甲苯暴露后,评估运动和认知功能。

结果

青少年甲苯暴露并未改变Rotarod任务中的运动学习(出生后第58天),也未改变Morris水迷宫中空间学习的获取、反转或保持(出生后第55 - 64天)。相比之下,它延迟了成年期(出生后第57 - 100天)对蔗糖(5% w/v)的工具性反应的获取,并损害了操作性反转学习以及线索诱导的蔗糖寻求行为的恢复。

结论

本研究表明,青春期接触滥用浓度的甲苯会导致工具性学习方面的特定损伤,而不会改变青春期晚期/成年早期的运动功能和空间学习。我们的数据表明,青少年吸入剂滥用后可能会出现奖励处理的持续改变。

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