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大鼠尾状核前壳和后壳脑片诱发多巴胺外流的区域差异。

Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen.

作者信息

Patel J, Trout S J, Kruk Z L

机构信息

Department of Pharmacology, Queen Mary and Westfield College, London, UK.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1992 Sep;346(3):267-76. doi: 10.1007/BF00173539.

Abstract

Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mumol/l DA) than in the pCPu (0.12 mumol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 Hz: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc). Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D2 receptor antagonists metoclopramide or (-)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms. These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

利用碳纤维微电极对大鼠脑片进行快速循环伏安法检测,以研究尾状核壳核前部(aCPu)10个不同位点和尾状核壳核后部(pCPu)10个位点电诱发多巴胺(DA)释放的区域差异。对于每个位点,单脉冲(1P)刺激和以50Hz频率施加的25个脉冲串(25P/50Hz)均可诱发DA溢出。1P诱发的aCPu峰值DA释放量(0.19μmol/l DA)比pCPu(0.12μmol/l DA)约高58%,但在两个区域内均未显示出内外侧差异。25P/50Hz诱发的峰值DA释放量相对于1P释放量在两个区域间也有所不同;aCPu主要包含低比率(25P/50Hz:1P)位点,范围为1.47至3.71,而在pCPu中这些比率更高,范围为2.73至9.40,且在pCPu的背内侧区域特别高。在aCPu低比率位点检测到的释放量对频率(10至500Hz)或一串脉冲中的脉冲数(5至20)几乎没有依赖性。相比之下,pCPu高比率位点诱发的DA释放量以脉冲和频率依赖性方式响应,最大比率(约为1P的8倍)出现在20P/20Hz时。有趣的是,在pCPu中获得的频率响应关系类似于伏隔核(NAc)中观察到的情况。伏安法证据和使用选择性再摄取阻滞剂的实验表明,在我们的研究中仅测量到了DA,5-羟色胺(5-HT)对pCPu高比率位点检测到的频率依赖性释放模式没有显著贡献,而pCPu中的纹状体5-HT浓度最高。使用选择性D2受体拮抗剂甲氧氯普胺或(-)舒必利的实验表明,在我们的实验条件下,aCPu中的DA释放不受DA自身受体激活的调节。相比之下,在pCPu的高比率位点,当刺激持续超过约1000ms时,确实发生了自身受体调节。这些观察结果支持了尾状核壳核在诱发DA释放的频率特征方面是异质性组织的这一概念。在这些条件下控制频率依赖性释放的因素可能是A10神经支配的函数,因为高比率释放位点出现在这种神经支配密度最大的区域,例如背内侧pCPu。这一观点得到了以下观察结果的支持,即在NAc中也发现了高比率释放位点,而NAc主要接收来自A10区域的多巴胺能纤维。(摘要截短至400字)

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