Yamamoto B K, Freed C R
Nature. 1982 Jul 29;298(5873):467-8. doi: 10.1038/298467a0.
Despite considerable knowledge about brain dopamine in drug-induced and pathological states, the dynamic relationship of dopamine to voluntary motor behaviour is not established. In an effort to produce selective, lateralized changes in brain dopamine metabolism associated with movement, we have now developed an animal model in which normal rats were trained to circle for a sucrose/water reward. Turning direction was randomly assigned. The effect of circling on dopamine metabolism was studied by killing animals during the reinforcement period and measuring caudate dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations in both sides of brain. Prior to turning, caudate dopamine and DOPAC levels were the same bilaterally. By contrast, animals killed after 20 min of circling showed a 67% increase in dopamine and a 46% increase in DOPAC concentrations in the caudate contralateral to the turning direction while the ipsilateral caudate showed no concentration changes. Such a rapid, massive unilateral increase in caudate dopamine metabolism suggests that dopamine neurones in contralateral caudate are selectively activated during circling behaviour. This model should be useful for further study of the relationships between neurotransmitter activity, regional brain physiology and voluntary movement, without the need for drugs or brain lesions.
尽管在药物诱导和病理状态下对脑多巴胺已有相当多的了解,但多巴胺与自主运动行为之间的动态关系尚未确立。为了在与运动相关的脑多巴胺代谢中产生选择性的、偏侧化的变化,我们现在建立了一种动物模型,让正常大鼠经过训练以转圈的方式获取蔗糖/水奖励。转圈方向随机分配。通过在强化期处死动物并测量脑两侧尾状核多巴胺和二羟基苯乙酸(DOPAC)的浓度,研究了转圈对多巴胺代谢的影响。在开始转圈之前,双侧尾状核多巴胺和DOPAC水平相同。相比之下,转圈20分钟后处死的动物,其转向对侧尾状核中的多巴胺浓度增加了67%,DOPAC浓度增加了46%,而同侧尾状核的浓度没有变化。尾状核多巴胺代谢如此迅速、大量的单侧增加表明,在转圈行为期间,对侧尾状核中的多巴胺神经元被选择性激活。该模型无需使用药物或造成脑损伤,对于进一步研究神经递质活性、局部脑生理学和自主运动之间的关系应该是有用的。