Walker S C, Mikheenko Y P, Argyle L D, Robbins T W, Roberts A C
Department of Experimental Psychology, Downing Street, Cambridge CB2 3EB, UK.
Eur J Neurosci. 2006 Jun;23(11):3119-23. doi: 10.1111/j.1460-9568.2006.04826.x.
We have recently shown that serotonin in the primate orbitofrontal cortex (OFC) contributes to the flexible control of behaviour. 5,7-dihydroxytryptamine-induced 5-HT depletions of OFC impair performance on a serial reversal discrimination task [Clarke et al. (2004)Science, 304, 878-880]. The deficit is characterized by perseverative responding to the previously rewarded stimulus, a deficit similar to that seen following lesions of the intrinsic neurones of the OFC [Dias et al. (1996)Nature, 380, 69-72]. The effect is neurochemically selective as dopaminergic lesions of the OFC, induced by 6-hydroxydopamine, have no effect [Clarke et al. (2006)Cerebral Cortex]. In order to test for the generality of the effect of serotonin on orbitofrontal processing and, in particular, its effects on flexible behaviour, the present study investigated the effects of serotonin depletions of OFC on performance of another task dependent upon an intact OFC, the detour-reaching task [Wallis et al. (2001)European Journal of Neuroscience, 13, 1797-1808]. Successful performance of this task requires inhibition of the animal's prepotent response tendency to reach directly along its line of sight to the reward. Compared with sham-operated controls, we found that lesioned monkeys made significantly more barrier reaches directly along their line of sight to the visible reward during task acquisition. This finding provides further support for the role of prefrontal serotonin in inhibitory control processes specifically in tasks sensitive to OFC dysfunction.
我们最近发现，灵长类动物眶额叶皮质（OFC）中的血清素有助于行为的灵活控制。5,7-二羟基色胺诱导的OFC中5-羟色胺耗竭会损害连续反转辨别任务的表现[Clarke等人（2004年）《科学》，304卷，878 - 880页]。这种缺陷的特征是持续对先前奖励的刺激做出反应，这一缺陷类似于OFC内在神经元损伤后所见的缺陷[Dias等人（1996年）《自然》，380卷，69 - 72页]。这种效应在神经化学上具有选择性，因为6-羟基多巴胺诱导的OFC多巴胺能损伤没有影响[Clarke等人（2006年）《大脑皮层》]。为了测试血清素对眶额叶加工影响的普遍性，特别是其对灵活行为的影响，本研究调查了OFC血清素耗竭对另一项依赖完整OFC的任务——迂回够物任务表现的影响[Wallis等人（2001年）《欧洲神经科学杂志》，13卷，1797 - 1808页]。成功完成这项任务需要抑制动物直接沿视线方向伸手获取奖励的优势反应倾向。与假手术对照组相比，我们发现受损猴子在任务获取过程中直接沿视线越过障碍物去获取可见奖励的次数明显更多。这一发现进一步支持了前额叶血清素在抑制控制过程中的作用，特别是在对OFC功能障碍敏感的任务中。
