Latysheva N V, Raevskii K S
Laboratory for Neurochemical Pharmacology, Science Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.
Neurosci Behav Physiol. 2003 Feb;33(2):123-31. doi: 10.1023/a:1021761512252.
Considering data on the possible glutamatergic nature of the pathogenesis of schizophrenia, we attempted to model cognitive derangements in animals by chronic blockade of NMDA glutamate receptors. Wistar rats received daily s.c. injections of the non-competitive NMDA glutamate receptor antagonist MK-801 (0.05 mg/kg) from days 7 to day 49 of postnatal life. One day after the antagonist injections given on days 27 and 28 of life, animals of the experimental group showed decreased levels of spontaneous movement and orientational-investigative activity as compared with controls, where there was no change in the elevated locomotor reaction produced in response to the direct action of MK-801. These animals showed decreases in the level of anxiety (on day 40 of life) and derangement in spatial learning with food reinforcement (days 50-54 of life). It is suggested that early neonatal blockade of NMDA glutamate receptors leads to the development in animals of disturbances to situational perception and assessment of incoming sensory information.
考虑到有关精神分裂症发病机制可能具有谷氨酸能性质的数据，我们试图通过慢性阻断NMDA谷氨酸受体来在动物中模拟认知紊乱。从出生后第7天到第49天，Wistar大鼠每天皮下注射非竞争性NMDA谷氨酸受体拮抗剂MK-801（0.05mg/kg）。在出生后第27天和第28天给予拮抗剂注射后的一天，与对照组相比，实验组动物的自发运动水平和定向探究活动降低，而对照组对MK-801直接作用产生的高架运动反应没有变化。这些动物在出生后第40天焦虑水平降低，在食物强化的空间学习中出现紊乱（出生后第50 - 54天）。提示新生儿早期阻断NMDA谷氨酸受体会导致动物出现情境感知和传入感觉信息评估障碍。
