Kurumaji A, McCulloch J
Wellcome Surgical Institute, University of Glasgow, U.K.
Brain Res. 1990 Oct 29;531(1-2):72-82. doi: 10.1016/0006-8993(90)90759-5.
Local cerebral glucose utilisation was examined in 62 discrete regions of conscious rats following unilateral ibotenic acid lesion of the caudal entorhinal cortex, and subsequent pharmacological challenge with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Fourteen days after unilateral lesion of the entorhinal cortex, there were no significant alterations in local cerebral glucose use except within the lesioned entorhinal cortex (reduced by 31% compared to sham-operated control animals). In sham-operated animals, systemic administration of MK-801 (0.5 mg/kg, i.v.) induced anatomically organised alterations in glucose use with increases in olfactory areas, subicular complex and some limbic areas (posterior cingulate cortex, mammillary body and anteroventral thalamic nucleus), and decreases in the inferior colliculus and neocortex (auditory, sensory-motor, somatosensory and frontal cortices). In animals with unilateral entorhinal cortex lesions, the metabolic response to MK-801 differed significantly from the response to the drug in sham-lesioned animals in a number of regions, viz. hippocampus, molecular layer (ipsilateral to lesion), entorhinal cortex (ipsilateral), dentate gyrus (ipsilateral), presubiculum (bilateral), parasubiculum (bilateral) and nucleus accumbens (bilateral). The ability of MK-801 to reduce glucose use in the neocortex was not altered by entorhinal cortex lesion. These data suggest that the functional consequences of non-competitive NMDA receptor blockade are dependent in some areas upon the integrity of the perforant pathway from the entorhinal cortex to the hippocampus.
在清醒大鼠的62个离散区域检测局部脑葡萄糖利用情况，这些大鼠接受了尾侧内嗅皮质的单侧鹅膏蕈氨酸损伤，随后用非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂马来酸（+）-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（MK-801）进行药理学激发。在内嗅皮质单侧损伤14天后，除了损伤的内嗅皮质内（与假手术对照动物相比降低了31%），局部脑葡萄糖利用没有显著改变。在假手术动物中，静脉注射MK-801（0.5mg/kg）可诱导葡萄糖利用出现解剖学上有组织的改变，嗅觉区域、海马旁回复合体和一些边缘区域（后扣带回皮质、乳头体和丘脑前腹核）增加，而下丘和新皮质（听觉、感觉运动、躯体感觉和额叶皮质）减少。在单侧内嗅皮质损伤的动物中，在多个区域，即海马、分子层（损伤同侧）、内嗅皮质（同侧）、齿状回（同侧）前下托（双侧）、下托旁区（双侧）和伏隔核（双侧），对MK-801的代谢反应与假损伤动物对该药物的反应有显著差异。内嗅皮质损伤并未改变MK-801降低新皮质葡萄糖利用的能力。这些数据表明，在某些区域，非竞争性NMDA受体阻断的功能后果取决于从内嗅皮质到海马的穿通通路的完整性。
