Department of Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam, Center for Neurogenomic and Cognitive Research, VU University, Amsterdam, The Netherlands; Sylics (Synaptologics BV), Amsterdam, The Netherlands.
Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Eur J Pharmacol. 2016 Jun 15;781:157-63. doi: 10.1016/j.ejphar.2016.04.015. Epub 2016 Apr 11.
Impulse control disturbances are key features of various neuropsychiatric and neurological disorders, such as attention-deficit/hyperactivity disorder, drug addiction, Parkinson disease and schizophrenia. Whereas over the last years accumulating evidence has highlighted monoaminergic modulation of the processes underlying impulse control, investigating novel mechanisms beyond monoamines may provide new intervention strategies to ameliorate impulse control disturbances. Recent work has associated the neuregulin (Nrg)-ErbB pathway with several neuropsychiatric diseases, as well as indicated its involvement in murine measures of impulse control. The aim of the present study was to investigate whether this Nrg-ErbB signaling pathway also modulates impulsive action in rats. To this end, a group of rats was trained in the 5-choice serial reaction time task (5-CSRTT), an operant paradigm that provides measures of visuospatial attention and inhibitory control processes. Upon stable baseline performance, the ErbB tyrosine kinase receptor inhibitor JNJ-28871063 (JNJ) was intracranially infused into the medioprefrontal cortex prior to test sessions. Results showed that JNJ dose-dependently improved measures of impulsive action. Importantly, other measures in the 5-CSRTT reflecting visuospatial attention or aspects of motivational behavior were not altered by JNJ. In conclusion, the present data strengthen a role for the Nrg-ErbB4 pathway in the prefrontal cortex in cognitive functioning, and in particular point towards involvement in the processes underlying impulse control.
冲动控制障碍是各种神经精神和神经疾病的主要特征，如注意缺陷/多动障碍、药物成瘾、帕金森病和精神分裂症。近年来，越来越多的证据表明单胺能调节冲动控制的相关过程，而研究单胺以外的新机制可能为改善冲动控制障碍提供新的干预策略。最近的工作将神经调节蛋白（Nrg）-表皮生长因子受体（ErbB）途径与几种神经精神疾病联系起来，并表明其参与了啮齿动物的冲动控制测量。本研究的目的是调查 Nrg-ErbB 信号通路是否也调节大鼠的冲动行为。为此，一组大鼠在 5 选择连续反应时间任务（5-CSRTT）中接受训练，这是一种操作性范式，可提供视觉空间注意和抑制控制过程的测量。在稳定的基线表现后，将 ErbB 酪氨酸激酶受体抑制剂 JNJ-28871063（JNJ）颅内输注到中前额叶皮层，然后进行测试。结果表明，JNJ 剂量依赖性地改善了冲动行为的测量。重要的是，JNJ 并未改变 5-CSRTT 中反映视觉空间注意或动机行为方面的其他测量值。总之，本数据强化了 Nrg-ErbB4 通路在前额叶皮层认知功能中的作用，特别是表明其参与了冲动控制的相关过程。
