Archer T, Danysz W, Fredriksson A, Jonsson G, Luthman J, Sundström E, Teiling A
Department of Psychoneuropharmacology, R & D Laboratories, Astra Alab AB, Södertälje, Sweden.
Pharmacol Biochem Behav. 1988 Oct;31(2):357-64. doi: 10.1016/0091-3057(88)90358-9.
Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.
进行了三项实验，以研究新生大鼠脑室内注射6-羟基多巴胺（6-OHDA）诱导的多巴胺（DA）耗竭对自发运动活动测量的影响。还研究了在奥尔顿放射状臂迷宫中获取食物奖励的工具性学习以及从大型圆形水迷宫中逃脱的学习。通过在改良的放射状臂迷宫中直接观察大鼠以及使用配备光电管装置的自动测试笼来测量运动活动。经6-OHDA处理的大鼠表现出显著且持久的运动（行走）活动增加以及总活动量增加。在每个60分钟测试期的最初20分钟内，经6-OHDA处理的大鼠的竖毛活动明显少于经载体处理的大鼠。然而，在这些60分钟测试期的后半段，经6-OHDA处理的大鼠的竖毛活动明显多于经载体处理的大鼠。在获取奔跑反应以获得放置在放射状臂迷宫的8个臂中的每个臂中的8个食物颗粒时，6-OHDA大鼠的获取过程延迟，这通过获取所有八个颗粒的潜伏期和访问的臂数来衡量。经6-OHDA处理的大鼠完全未能学会莫里斯型游泳迷宫任务，该任务要求它们在圆形水箱中找到水面下的一个平台。神经化学分析表明，几个前脑区域存在严重的DA耗竭。本研究结果进一步表明，这种DA耗竭状态作为轻微脑功能障碍综合征动物模型具有潜在可能性。
