Robbins T W, Giardini V, Jones G H, Reading P, Sahakian B J
Department of Experimental Psychology, University of Cambridge, U.K.
Behav Brain Res. 1990 May 28;38(3):243-61. doi: 10.1016/0166-4328(90)90179-i.
Three experiments compared the effects of dopamine depletion from the caudate-putamen (CAUD; dorsal striatum) or nucleus accumbens septi (NAS; ventral striatum), or a systemically administered dopamine receptor antagonist (alpha-flupenthixol) on the acquisition and performance of a conditional discrimination task involving temporal frequency. In Expt. 1, rats receiving 6-hydroxydopamine (6-OHDA) lesions of the CAUD were impaired in the acquisition of a visual version of the task, and rats with 6-OHDA lesions of the NAS were not reliably impaired. Even when the rats with CAUD lesions had acquired the discrimination, they were still significantly slower to collect earned food pellets. Both CAUD and NAS lesions reduced a bias to respond to the faster of the two discriminative stimuli. In Expt. 2, rats with 6-OHDA lesions of CAUD were markedly impaired in their accuracy and speed of responding when they had been trained to criterion preoperatively. These effects could not be mimicked in controls by prefeeding (which had only minor effects on performance). Rats with 6-OHDA-induced lesions of the NAS were unimpaired in either visual or auditory discrimination performance, but were slower to extinguish responding than controls. In Expt. 3, alpha-flupenthixol (0.1-0.56 mg/kg, i.p.) produced dose-dependent impairments in both latency to respond and choice accuracy in visual and auditory versions of the task. In conjunction with other results, these data suggest that (1) dopamine receptor blockade and central dopamine depletion can impair discrimination performance under certain conditions (2) dopamine depletion from the ventral and dorsal striatum, respectively, have dissociable effects on behaviour controlled by conditioned reinforcers and discriminative stimuli and (3) the disruption of discrimination performance by dorsal striatal dopamine depletion is probably attributable to several factors.
三项实验比较了尾状核-壳核（CAUD；背侧纹状体）或伏隔核（NAS；腹侧纹状体）多巴胺耗竭，或系统给予多巴胺受体拮抗剂（α-氟哌噻吨）对涉及时间频率的条件性辨别任务的习得和表现的影响。在实验1中，接受CAUD 6-羟基多巴胺（6-OHDA）损伤的大鼠在视觉版任务的习得方面受损，而接受NAS 6-OHDA损伤的大鼠未出现可靠的损伤。即使CAUD损伤的大鼠已经习得辨别，它们收集奖励食物颗粒的速度仍然明显较慢。CAUD和NAS损伤均降低了对两种辨别性刺激中较快刺激做出反应的偏向性。在实验2中，术前已训练至标准的CAUD 6-OHDA损伤大鼠在反应准确性和速度方面明显受损。通过预喂（对表现仅有轻微影响）无法在对照组中模拟这些效应。NAS 6-OHDA诱导损伤的大鼠在视觉或听觉辨别表现方面未受损，但比对照组更慢地消除反应。在实验3中，α-氟哌噻吨（0.1 - 0.56毫克/千克，腹腔注射）在任务的视觉和听觉版本中，对反应潜伏期和选择准确性均产生剂量依赖性损伤。结合其他结果，这些数据表明：（1）多巴胺受体阻断和中枢多巴胺耗竭在某些条件下会损害辨别表现；（2）分别来自腹侧和背侧纹状体的多巴胺耗竭，对由条件性强化物和辨别性刺激控制的行为具有可分离的影响；（3）背侧纹状体多巴胺耗竭对辨别表现的破坏可能归因于多种因素。
