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青少年哌甲酯自我给药对条件性奖励反应、安非他命诱导的运动活动和神经元激活的影响。

The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation.

机构信息

Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S3G3, Canada.

出版信息

Psychopharmacology (Berl). 2010 Feb;208(3):455-68. doi: 10.1007/s00213-009-1745-7. Epub 2009 Dec 18.

Abstract

BACKGROUND

Abuse of methylphenidate (Ritalin) is rising, particularly during adolescence and early adulthood, but the long-term effects of its abuse during adolescence are unclear.

METHODS

In experiment 1, we examined the effect of adolescent methylphenidate self-administration (0.0625 mg/infusion), as compared with cocaine self-administration (0.125 mg/infusion), under a fixed ratio 1 schedule of reinforcement in male Sprague-Dawley rats during adolescence (postnatal day (PND) 32-47) on adult dopamine-mediated behaviors (PND >70). These included responding for a conditioned reward (CR), a measure of incentive motivation, and amphetamine-induced locomotor activity. In experiment 2, we aimed to replicate and enhance the effects observed in experiment 1, and we also examined the effects of methylphenidate self-administration during adolescence on adult amphetamine-induced zif268 messenger ribonucleic acid (mRNA) expression.

RESULTS

Adolescent rats self-administered both cocaine and methylphenidate. There was no effect of adolescent drug self-administration on adult baseline or amphetamine-induced responding for a CR. However, both adolescent methylphenidate and cocaine self-administration increased amphetamine-induced locomotion. Adolescent methylphenidate self-administration also enhanced amphetamine-induced zif268 mRNA expression in the nucleus accumbens.

CONCLUSIONS

Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation.

摘要

背景

哌醋甲酯(利他林)的滥用呈上升趋势,尤其是在青少年和成年早期,但在青春期滥用哌醋甲酯的长期影响尚不清楚。

方法

在实验 1 中,我们在雄性 Sprague-Dawley 大鼠中,在青春期(出生后第 32-47 天),比较了在固定比率 1 强化程序下,自我给予哌醋甲酯(0.0625 毫克/输注)与自我给予可卡因(0.125 毫克/输注)对成年多巴胺介导的行为(PND > 70)的影响。这些行为包括对条件性奖励(CR)的反应,这是一种激励动机的衡量标准,以及安非他命诱导的运动活动。在实验 2 中,我们旨在复制和增强实验 1 中观察到的效果,并且还研究了青春期自我给予哌醋甲酯对成年安非他命诱导的zif268 信使核糖核酸(mRNA)表达的影响。

结果

青春期大鼠自我给予可卡因和哌醋甲酯。青春期药物自我给予对成年基础或安非他命诱导的 CR 反应没有影响。然而,青春期哌醋甲酯和可卡因自我给予都增加了安非他命诱导的运动。青春期哌醋甲酯自我给予也增强了伏隔核中安非他命诱导的zif268 mRNA 表达。

结论

我们的发现表明,在青春期反复、行为相关的哌醋甲酯暴露增强了对安非他命的运动刺激和神经元激活作用的反应性,但不增强激励动机。

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