IONTOPHORETICALLY ADMINISTERED DRUGS ACTING AT THE N-METHYL-D-ASPARTATE RECEPTOR MODULATE BURST FIRING IN A9-DOPAMINE NEURONS IN THE RAT
IONTOPHORETICALLY ADMINISTERED DRUGS ACTING AT THE N-METHYL-D-ASPARTATE RECEPTOR MODULATE BURST FIRING IN A9-DOPAMINE NEURONS IN THE RAT
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DOI：
10.1002/syn.890100208
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发表时间：
1992-02-01
期刊：
影响因子：
2.3
通讯作者：
CLARK, D
中科院分区：
文献类型：
--
作者：
OVERTON, P;CLARK, D
采用细胞外单单位记录和离子电泳技术研究了n -甲基- d -天冬氨酸（NMDA）和NMDA竞争性拮抗剂(+/-)-4-（3-磷酸丙基）-2-哌嗪羧酸（CPP）对大鼠A9多巴胺（DA）神经元放电速率和放电模式的影响。NMDA的施用产生了剂量依赖性的射速增加（在最高射电流下高达基线的近300%），这可以被离子透性CPP阻断。低电流（< 10 nA）足以诱导某些神经元的去极化失活。除了对射击速率的影响外，NMDA还引起了爆发射击的急剧增加，这也是剂量依赖性的；细胞产生更多的脉冲，每次脉冲由更多的尖峰组成。唯一不受影响的爆发形态测量方面是平均爆发间隔时间。所有非爆裂细胞（n = 10）经药物转化为爆裂放电。单独使用CPP可减少爆发射击，但不影响射击速率。这些数据表明，一种张力性的兴奋性氨基酸输入到A9 DA神经元中，负责在体内诱导突发放电，这种输入似乎通过NMDA受体起作用，可能是由于它与Ca2+离子载体的联系。
Extracellular single-unit recording and iontophoresis were used to examine the effect of N-methyl-D-aspartate (NMDA) and the competitive NMDA antagonist (+/-)-4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) on the firing rate and firing pattern of A9 dopamine (DA) neurons in the rat. Administration of NMDA produced a dose-dependent increase in firing rate (up to nearly 300% of baseline at the highest ejection current), which could be blocked by iontophoretic CPP. Low currents (< 10 nA) were sufficient to induce apparent depolarisation inactivation in some neurons. In addition to this effect on firing rate, NMDA also caused a dramatic increase in burst firing, which was also dose dependent; cells made more bursts, and each burst consisted of more spikes. The only measured aspect of burst morphology that was not affected was the mean burst interspike interval. All nonbursting cells (n = 10) were converted to burst firing by the drug. CPP administered alone was found to reduce burst firing, without affecting the firing rate. These data suggest that a tonically active excitatory amino acid input to A9 DA neurons is responsible for inducing burst firing in vivo and that this input seems to operate via the NMDA receptor, possibly by virtue of its link to a Ca2+ ionophore.