Ballester González Javier, Dvorkin-Gheva Anna, Silva Charmaine, Foster Jane A, Szechtman Henry
aDepartment of Psychiatry, Yale University, New Haven, Connecticut, USA bDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Behav Pharmacol. 2015 Feb;26(1-2):200-16. doi: 10.1097/FBP.0000000000000112.
To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization.
为研究伏隔核核心区（NAc）在喹吡罗诱导的强迫性检查行为发展中的作用，将大鼠分为接受NAc兴奋性损伤组或假损伤组，并分别注射喹吡罗（0.5mg/kg）或生理盐水；通过10次每两周进行一次的测试来监测检查行为的发展。结果显示，即使在NAc损伤后，喹吡罗仍能诱导强迫性检查行为，这表明喹吡罗产生的致病作用并非源于NAc。尽管NAc损伤并未阻止强迫性检查行为的诱导，但却改变了其发展速度，这表明NAc通常对强迫性检查行为的诱导有一定作用。接受NAc损伤并注射生理盐水的大鼠表现为多动，但未出现强迫性检查行为，这表明多动本身并不足以导致强迫性检查行为的发病机制。研究提出，强迫性检查行为是安全动机系统过度输出的结果，而NAc作为一个神经枢纽，协调该动机系统神经模块的有序活动。有证据表明，强迫性检查行为发病机制的神经生物学条件有两个方面：多巴胺D2/D3受体的激活而无D1样受体的同时刺激，以及与喹吡罗诱导的敏感化相关的长期可塑性变化。
