Hauser Joachim, Reissmann Andreas, Sontag Thomas-A, Tucha Oliver, Lange Klaus W
Department of Experimental Psychology, University of Regensburg, 93040, Regensburg, Germany.
Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, The Netherlands.
Atten Defic Hyperact Disord. 2017 Dec;9(4):253-262. doi: 10.1007/s12402-017-0225-x. Epub 2017 Mar 14.
The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats' performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.
本研究的目的是评估神经毒素N-(2-氯乙基)-N-乙基-2-溴苄胺(DSP4)对大鼠注意力的影响,该毒素能以剂量依赖的方式使去甲肾上腺素能神经末梢耗竭,大鼠注意力通过五选择连续反应时任务(5CSRTT)进行测量。此外,我们研究了阿托莫西汀是否能逆转DSP4治疗的效果。阿托莫西汀是一种选择性去甲肾上腺素再摄取抑制剂,已被证明对治疗注意力缺陷多动障碍有效。将Wistar大鼠训练进行5CSRTT,并给予三种剂量之一的DSP4(10、20或50mg/kg)或生理盐水进行处理。DSP4处理后,给大鼠注射三种剂量的阿托莫西汀(0.1, 0.5或1mg/kg)或生理盐水,并在5CSRTT中进行测试。DSP4处理导致活动减少以及与5CSRTT中注意力相关参数的表现下降。这些损伤是否归因于注意力缺陷或探索行为和活动的变化仍有待研究。无论是否进行DSP4处理,阿托莫西汀处理对大鼠的表现均无有益影响。本研究结果支持去甲肾上腺素在调节注意力过程中的作用,并呼吁未来开展关于阿托莫西汀对大鼠注意力影响的研究。