Zhang J, Chiodo L A, Freeman A S
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan.
J Pharmacol Exp Ther. 1994 Apr;269(1):313-21.
In vivo electrophysiological recording methods were used to evaluate the effects of selective and nonselective agonists for excitatory amino acid (EAA) receptor subtypes on the activity of dopaminergic (DA) and nondopaminergic (non-DA) neurons in the substantia nigra of chloral hydrate-anesthetized rats. Microiontophoretic administration of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), 2-carboxy-4-(1-methyl-ethenyl)-3-pyrrolidinacetate (kainate), N-methyl-D-aspartate (NMDA) and glutamate excited neurons with an apparent rank order of potency of AMPA = kainate = glutamate > NMDA on DA neurons, and AMPA = kainate > glutamate = NMDA on non-DA neurons. These agonists also changed the firing pattern of DA neurons, which displayed an increase in burst-firing and a reduction in the regularity of the firing pattern. Regularity of firing was indexed by the variation coefficient of a sample of interspike intervals. The apparent potencies of the four agonists to increase burst-firing and variation coefficient were similar to their potencies to increase neuronal firing rate. Blockade of NMDA receptor function by coiontophoresis of 5R,10S-(+/-)-5-methyl-10,11-dihydro-5H-dibenzo[and]cyclohepten-5,1 0-imine hydrogen maleate (MK-801), a selective noncompetitive NMDA antagonist, did not alter kainate-induced changes in firing rate and firing pattern, which indicated that kainate-induced increases in burst-firing were not dependent on concomitant NMDA receptor activation by endogenous excitatory amino acid.(ABSTRACT TRUNCATED AT 250 WORDS)
采用体内电生理记录方法,评估兴奋性氨基酸(EAA)受体亚型的选择性和非选择性激动剂对水合氯醛麻醉大鼠黑质中多巴胺能(DA)和非多巴胺能(非DA)神经元活性的影响。通过微离子电泳给予(±)-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)、2-羧基-4-(1-甲基乙烯基)-3-吡咯烷乙酸(海人酸)、N-甲基-D-天冬氨酸(NMDA)和谷氨酸,可兴奋神经元,对DA神经元的效力顺序明显为AMPA = 海人酸 = 谷氨酸 > NMDA,对非DA神经元的效力顺序为AMPA = 海人酸 > 谷氨酸 = NMDA。这些激动剂还改变了DA神经元的放电模式,表现为爆发性放电增加,放电模式的规律性降低。放电规律性通过峰间间隔样本的变异系数来衡量。四种激动剂增加爆发性放电和变异系数的表观效力与其增加神经元放电频率的效力相似。通过共同离子电泳给予选择性非竞争性NMDA拮抗剂5R,10S-(±)-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸氢盐(MK-801)阻断NMDA受体功能后,并未改变海人酸诱导的放电频率和放电模式变化,这表明海人酸诱导的爆发性放电增加不依赖于内源性兴奋性氨基酸伴随的NMDA受体激活。(摘要截短于250字)