Dai H, Carey R J
VA Medical Center, Syracuse, NY 13210.
Behav Brain Res. 1994 Jun 30;62(2):149-56. doi: 10.1016/0166-4328(94)90022-1.
Using a modified open-field method, we assessed the effects of MK-801 (0.01 to 0.3 mg/kg) on locomotion and on attention to a stimulus object located in a computer-generated central zone (CZ). The CZ comprised 1/9 of the open-field floor area and was monitored independently from the rest of the area. Intermittently, a 4 x 4 x 2 cm block was placed in the CZ. In 10-min trials, non-drug tests showed that the presence of the stimulus object repeatedly and consistently increased the rats' visit duration in the CZ as compared with tests when the object was absent. Locomotor activity and entries to the CZ were unaffected by the object. MK-801 induced dose dependent hyperlocomotion and increased CZ entries and, most important, a dose dependent decrease in the animal's response to the stimulus object in the CZ. The present investigation suggests that MK-801 impacts upon two major functions; (a) a blockade of processing of attentional information from the external world and (b) activation of locomotor response systems. These findings are consistent with the hypothesis that blockade of glutamate neurotransmission by MK-801 impairs the flow of information from the external world to response mechanisms in the striatum. The present study also suggests that MK-801's potential as a therapeutic agent for motoric activation in the treatment for Parkinson's disease would be contraindicated by its disruptive influence upon attention processing functions.
我们采用改良的旷场法，评估了MK - 801（0.01至0.3毫克/千克）对运动以及对位于计算机生成的中央区域（CZ）内的刺激物体的注意力的影响。中央区域占旷场地面面积的1/9，并与该区域的其余部分独立监测。间歇性地，将一个4×4×2厘米的方块放置在中央区域。在10分钟的试验中，非药物测试表明，与物体不存在时的测试相比，刺激物体的存在反复且持续地增加了大鼠在中央区域的停留时间。运动活动和进入中央区域的次数不受物体的影响。MK - 801诱导剂量依赖性的运动亢进，增加了进入中央区域的次数，最重要的是，剂量依赖性地降低了动物对中央区域内刺激物体的反应。本研究表明，MK - 801影响两种主要功能；（a）阻断来自外部世界的注意力信息的处理，以及（b）激活运动反应系统。这些发现与以下假设一致，即MK - 801对谷氨酸神经传递的阻断会损害从外部世界到纹状体反应机制的信息流。本研究还表明，MK - 801作为帕金森病治疗中运动激活治疗剂的潜力将因其对注意力处理功能的破坏性影响而受到禁忌。
