MONITORING THE STIMULATED RELEASE OF DOPAMINE WITH INVIVO VOLTAMMETRY .2. CLEARANCE OF RELEASED DOPAMINE FROM EXTRACELLULAR FLUID

MONITORING THE STIMULATED RELEASE OF DOPAMINE WITH INVIVO VOLTAMMETRY .2. CLEARANCE OF RELEASED DOPAMINE FROM EXTRACELLULAR FLUID
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DOI:
10.1111/j.1471-4159.1984.tb00936.x
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发表时间:
1984-01-01
影响因子:
4.7
通讯作者:
WIGHTMAN, RM
WIGHTMAN, RM
中科院分区:
医学2区
文献类型:
--
作者:
EWING, AG;WIGHTMAN, RM

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将微伏安电极植入麻醉大鼠的四体核,用于监测电刺激内侧前脑束后多巴胺[DA]的释放。这些电极由未改性的碳纤维制成,并已用于正常的脉冲伏安法。当刺激开始时,DA出现在电极附近,当刺激终止时,DA几乎立即消失。有效扩散距离< 100 μ m。使用液相色谱电化学检测的尸检分析表明,以这种方式释放的DA被代谢为3,4-二羟基苯乙酸(DOPAC);然而,在刺激后的几秒钟内,细胞外液中没有观察到电化学物质。此外,DA神经元摄取的抑制剂、安非他明(1.8或15 mg. kg-1)或苯扎托品(25 mg. kg-1),或DA代谢,帕吉林(150 mg. kg-1)或托酚酮(100 mg. kg-1)并不显著影响DA从细胞外液中消失的速率,尽管它们可以影响释放的量。DA不能在细胞外液中自由扩散,因为存在神经元摄取机制,其将DA从细胞外液清除到神经元池中,在神经元池中发生DOPAC的代谢。在电刺激上行纤维的过程中可以观察到DA,因为神经元和神经元摄取系统在这些短时间尺度上无法去除。
Microvoltammetric electrodes implanted in the cuadate nucleus of the anesthetized rat were used to monitor dopamine [DA] released following electrical stimulation of the medial forebrain bundle. These electrodes are fabricated from unmodified carbon fibers and have been used with normal pulse voltammetry. DA appears in the vicinity of the electrode when the stimulation is initiated, and disappears almost immediately when the stimulation is terminated. The effective diffusion distance is < 100 .mu.m. Postmortem analysis using liquid chromatography with electrochemical detection shows that DA released in this manner is metabolized to 3,4-dihydroxyphenylacetic acid (DOPAC); however, neither substance is observed electrochemically in the extracellular fluid within seconds after the stimulation. In addition, inhibitors of neuronal uptake of DA, amphetamine (1.8 or 15 mg .cntdot. kg-1) or benztropine (25 mg .cntdot. kg-1), or of DA metabolism, pargyline (150 mg .cntdot. kg-1) or tropolone (100 mg .cntdot. kg-1) do not significantly affect the rate at which DA disappears from extracellular fluid, although they can affect the amount released. DA cannot freely diffuse in the extracellular fluid because an extraneuronal uptake mechanism exists that clears DA from extracellular fluid into an extraneuronal pool where metabolism to DOPAC occurs. DA can be observed during electrical stimulation of the ascending fibers because neuronal and extraneuronal uptake systems are unable to removed on these short time scales.