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The utility of rat models of impulsivity in developing pharmacotherapies for impulse control disorders

机译:大鼠冲动模型在开发控制冲动障碍的药物疗法中的用途

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摘要

High levels of impulsive behaviours are a clinically significant symptom in a range of psychiatric disorders, such as attention deficit hyperactivity disorder, bipolar disorder, personality disorders, pathological gambling and substance abuse. Although often measured using questionnaire assessments, levels of different types of impulsivity can also be determined using behavioural tests. Rodent analogues of these paradigms have been developed, and similar neural circuitry has been implicated in their performance in both humans and rats. In the current review, the methodology underlying the measurement of different aspects of impulsive action and choice are considered from the viewpoint of drug development, with a focus on the continuous performance task (CPT), stop-signal task (SST), goo-go and delay-discounting paradigms. Current issues impeding translation between animal and human studies are identified, and comparisons drawn between the acute effects of dopaminergic, noradrenergic and serotonergic compounds across species. Although the field could benefit from a more systematic determination of different pharmacological agents across paradigms, there are signs of strong concordance between the animal and human data. However, the type of impulsivity measured appears to play a significant role, with the SST and delay discounting providing more consistent effects for dopaminergic drugs, while the CPT and SST show better predictive validity so far for serotonergic and noradrenergic compounds. Based on the available data, it would appear that these impulsivity models could be used more widely to identify potential pharmacotherapies for impulse control disorders. Novel targets within the glutamatergic and serotonergic system are also suggested.LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit
机译:高水平的冲动行为是一系列精神疾病的临床上重要症状,例如注意力缺陷多动障碍,双相情感障碍,人格障碍,病理性赌博和药物滥用。尽管通常使用问卷调查评估来衡量,但也可以使用行为测试来确定不同类型的冲动水平。已经开发出了这些范例的啮齿类动物类似物,并且类似的神经回路也参与了它们在人类和大鼠中的表现。在当前的审查中,从药物开发的角度考虑了测量冲动行为和选择不同方面的基础方法,重点是连续执行任务(CPT),停止信号任务(SST),执行/否去和延迟折扣范例。确定了阻碍动物研究与人类研究之间转换的当前问题,并比较了跨物种的多巴胺能,去甲肾上腺素能和血清素能化合物的急性作用。尽管可以通过跨范式更系统地确定不同药理学药物来受益于该领域,但动物和人类数据之间存在强烈一致性的迹象。但是,测量的冲动类型似乎起着重要作用,SST和延迟贴现为多巴胺能药物提供了更一致的效果,而CPT和SST迄今为止对血清素能和去甲肾上腺素能化合物显示出更好的预测效度。根据现有数据,这些冲动模型似乎可以更广泛地用于识别潜在的冲动控制障碍药物治疗。还提出了在谷氨酸能和5-羟色胺能系统中的新靶标。链接的文章本文是有关转化神经药理学的主题问题的一部分。要查看本期中的其他文章,请访问

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