Departments of Anatomy and Neurobiology, University of Maryland, Baltimore, MD, USA.
Int J Neuropsychopharmacol. 2013 Jul;16(6):1295-307. doi: 10.1017/S146114571200154X. Epub 2013 Jan 29.
Obsessive compulsive disorder (OCD) is a psychiatric condition defined by intrusive thoughts (obsessions) associated with compensatory and repetitive behaviour (compulsions). However, advancement in our understanding of this disorder has been hampered by the absence of effective animal models and correspondingly analysis of the physiological changes that may be present in these models. To address this, we have evaluated two current rodent models of OCD; repeated injection of dopamine D2 agonist quinpirole and repeated adolescent injection of the tricyclic agent clomipramine in combination with a behavioural paradigm designed to produce compulsive lever pressing. These results were then compared with their relative impact on the state of activity of the mesolimbic dopaminergic system using extracellular recoding of spontaneously active dopamine neurons in the ventral tegmental area (VTA). The clomipramine model failed to exacerbate compulsive lever pressing and VTA dopamine neurons in clomipramine-treated rats had mildly diminished bursting activity. In contrast, quinpirole-treated animals showed significant increases in compulsive lever pressing, which was concurrent with a substantial diminution of bursting activity of VTA dopamine neurons. Therefore, VTA dopamine activity correlated with the behavioural response in these models. Taken together, these data support the view that compulsive behaviours likely reflect, at least in part, a disruption of the dopaminergic system, more specifically by a decrease in baseline phasic dopamine signalling mediated by burst firing of dopamine neurons.
强迫症（OCD）是一种精神疾病，其特征是存在侵入性思维（强迫观念），并伴有补偿性和重复性的行为（强迫行为）。然而，由于缺乏有效的动物模型，以及对这些模型中可能存在的生理变化的相应分析，我们对这种疾病的理解进展受到了阻碍。为了解决这个问题，我们评估了两种现有的 OCD 啮齿动物模型：反复注射多巴胺 D2 激动剂喹吡罗和反复在青春期注射三环抗抑郁药氯米帕明，同时结合一种设计用于产生强迫性按压杠杆的行为范式。然后，将这些结果与它们对腹侧被盖区（VTA）中自发活动的多巴胺神经元的细胞外记录所显示的中脑边缘多巴胺系统活动状态的相对影响进行比较。氯米帕明模型未能加重强迫性按压，并且氯米帕明处理的大鼠的 VTA 多巴胺神经元的爆发活动轻度减弱。相比之下，喹吡罗处理的动物表现出明显的强迫性按压增加，这与 VTA 多巴胺神经元爆发活动的实质性减少同时发生。因此，VTA 多巴胺活动与这些模型中的行为反应相关。总之，这些数据支持这样一种观点，即强迫行为可能至少部分反映了多巴胺系统的紊乱，更具体地说，是由于多巴胺神经元的爆发式放电介导的基础相位多巴胺信号的减少。
