Turner Karly M, Burne Thomas H J
Queensland Brain Institute, The University of Queensland, St Lucia, 4072, QLD, Australia.
Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD, 4077, Australia.
Psychopharmacology (Berl). 2016 Sep;233(18):3383-94. doi: 10.1007/s00213-016-4376-9. Epub 2016 Jul 28.
Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents.
This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats.
Sprague-Dawley rats were trained on the SDT prior to amphetamine challenge (0.1, 0.25, 0.75 and 1.25 mg/kg). This dose range was predicted to enhance and disrupt cognition with the effect differing between individuals depending on baseline performance.
Acute low dose amphetamine (0.1 and 0.25 mg/kg) improved accuracy, while the highest dose (1.25 mg/kg) significantly disrupted performance. The effects differed for low- and high-performing groups across these doses. The effect of amphetamine on accuracy was found to significantly correlate with baseline performance in rats.
This study demonstrates that improvement in attentional performance with systemic amphetamine is dependent on baseline accuracy in rats. Indicative of the inverted U-shaped relationship between dopamine and cognition, there was a baseline-dependent shift in performance with increasing doses of amphetamine. The SDT may be a useful tool for investigating individual differences in attention and response to psychostimulants in rodents.
注意力缺陷存在于一系列神经精神疾病中，如精神分裂症和注意力缺陷多动障碍。精神兴奋剂是治疗注意力缺陷的主要方法之一，但在临床前研究中，关于苯丙胺促认知作用的报道有限。因此，在测量啮齿动物的注意力时，可能需要开发新的任务来提高预测效度。
本研究旨在使用改良的信号检测任务（SDT）来确定苯丙胺是否以及在何种剂量下可以改善大鼠的注意力。
在给予苯丙胺（0.1、0.25、0.75和1.25mg/kg）刺激之前，对斯普拉格-道利大鼠进行SDT训练。预计该剂量范围会增强和干扰认知，其效果因个体的基线表现而异。
急性低剂量苯丙胺（0.1和0.25mg/kg）提高了准确性，而最高剂量（1.25mg/kg）则显著干扰了表现。在这些剂量下，低表现组和高表现组的效果有所不同。发现苯丙胺对准确性的影响与大鼠的基线表现显著相关。
本研究表明，全身性苯丙胺对注意力表现的改善取决于大鼠的基线准确性。这表明多巴胺与认知之间呈倒U形关系，随着苯丙胺剂量的增加，表现出现了基线依赖性变化。SDT可能是研究啮齿动物注意力个体差异以及对精神兴奋剂反应的有用工具。
