Integrating neural, neurochemical and molecular mechanisms of impulse control

冲动既是有益的，也是有害的人类特征，允许我们抓住宝贵的机会或做出我们终生后悔的灾难性决定。高水平的冲动是双相情感障碍和注意力缺陷多动障碍(AD/HD)等精神障碍的关键症状。提高我们对冲动的生物学基础的理解，可以为这些疾病的本质提供宝贵的见解。最近的证据表明，神经递质去甲肾上腺素可能在冲动的调节中起重要作用，调节该系统活动的新型药物可能为治疗AD/HD提供刺激性药物的替代。去甲肾上腺素能活动的增加也被证明会在双相情感障碍患者中引发躁狂。我们最近发现，药物育亨宾可以增加大脑中去甲肾上腺素的水平，也可以增加大鼠的冲动反应。我们打算确定大脑中哪些区域的去甲肾上腺素能受体负责影响冲动行为的这种变化。我们希望利用这一知识，以及已知的其他药物对不同神经递质系统的影响，以了解改变脉冲控制的药物如何会聚在类似的细胞内信号通路上。这些信息可能会产生冲动的“分子足迹”，将行为与分子生物学联系起来，这最终可能会为冲动控制障碍的治疗开辟新的途径。

Impulsivity is both a beneficial and detrimental human characteristic, allowing us to seize a valuable opportunity or to make a disastrous decision we live to regret. A high level of impulsivity is a key symptom in psychiatric disorders such as bipolar disorder and attention-deficit hyperactivity disorder (AD/HD). Improving our understanding of the biological basis of impulsivity could provide valuable insight into the nature of these illnesses. Recent evidence suggests that the neurotransmitter noradrenaline may be important in the regulation of impulsivity, and novel drugs which modulate the activity of this system may offer alternatives to stimulant medication for AD/HD. Increases in noradrenergic activity have also been shown to trigger mania in bipolar patients. We have recently found that the drug yohimbine, which increases noradrenaline levels in the brain, also increases impulsive responding in rats. We intend to determine which noradrenergic receptors in which brain regions are responsible for effecting this change in impulsive behaviour. We wish to use this knowledge, together with what is known regarding the effects of other pharmacological agents active at different neurotransmitter systems, in order to understand how drugs which alter impulse control may converge on similar intracellular signaling pathways. Such information could generate a "molecular footprint" for impulsivity, linking behaviour to molecular biology, which could in time open up new avenues for therapeutic treatment for impulse control disorders.