Carter C J, Pycock C J
Brain Res. 1980 Jun 16;192(1):163-76. doi: 10.1016/0006-8993(80)91016-1.
The effects of 6-hydroxydopamine (6-OHDA) lesions of catecholamine terminals within the medial prefrontal cortex on spontaneous motor activity, dopamine (DA)-dependent stereotyped behaviour and subcortical dopamine turnover were investigated in the rat. Two types of lesions were examined, bilateral injection of 6-OHDA into the medial prefrontal cortex of untreated rats (6-OHDA alone), and bilateral injection of 6-OHDA into the medial prefrontal cortex of animals pretreated with the noradrenaline (NA) uptake blocking agent desmethylimipramine (6-OHDA/-DMI). Ten days after surgery the 6-OHDA lesions produced no significant change in spontaneous motor activity and had no overall effects on stereotyped behaviour induced by apomorphine or (+)-amphetamine. This lesion caused gross depletion of NA within the medial prefrontal cortex and curiously, elevated DA concentrations within this site. No changes in DA concentration were recorded within subcortical sites, although concentrations of DA metabolites within striatum and nucleus accumbens were reduced. In contrast, the 6-OHDA/DMI lesion of the medial prefrontal cortex significantly enhanced spontaneous motor activity and amphetamine-induced stereotyped behaviour. Apomorphine-induced stereotypy, on the other hand, was significantly reduced. Biochemically the lesion caused a large depletion of DA with relatively little loss of NA within the medial prefrontal cortex. In addition, from this and another study (ref. 33), increases in DA and its metabolite concentrations were measured in striatum and nucleus accumbens, together with an apparent increase in DA turnover within these subcortical sites. It is thus apparent that in the absence of a substantial portion of the DA innervation of the medial prefrontal cortex, with a largely intact NA innervation, there is an increase in motor activity and amphetamine-induced stereotypy which may be related to functional changes in DA activity within subcortical telencephalic structures. Such a finding might suggest that DA within the frontal cortex has a behaviourally inhibitory role in the rat, although further work is required to substantiate this.
研究了内侧前额叶皮质内儿茶酚胺终末的6-羟基多巴胺（6-OHDA）损伤对大鼠自发运动活动、多巴胺（DA）依赖性刻板行为及皮质下多巴胺周转率的影响。研究了两种类型的损伤，即向未处理大鼠的内侧前额叶皮质双侧注射6-OHDA（单独使用6-OHDA），以及向用去甲肾上腺素（NA）摄取阻断剂去甲丙咪嗪预处理的动物的内侧前额叶皮质双侧注射6-OHDA（6-OHDA/-DMI）。术后10天，6-OHDA损伤对自发运动活动无显著影响，对阿扑吗啡或（+）-苯丙胺诱导的刻板行为也无总体影响。该损伤导致内侧前额叶皮质内NA大量耗竭，奇怪的是，该部位的DA浓度升高。皮质下部位未记录到DA浓度变化，尽管纹状体和伏隔核内DA代谢物的浓度降低。相比之下，内侧前额叶皮质的6-OHDA/DMI损伤显著增强了自发运动活动和苯丙胺诱导的刻板行为。另一方面，阿扑吗啡诱导的刻板行为显著减少。生化方面，该损伤导致内侧前额叶皮质内DA大量耗竭，而NA损失相对较少。此外，从本研究及另一项研究（参考文献33）可知，纹状体和伏隔核内DA及其代谢物浓度升高，同时这些皮质下部位的DA周转率明显增加。因此，显然在内侧前额叶皮质大部分DA神经支配缺失而NA神经支配基本完整的情况下，运动活动增加以及苯丙胺诱导的刻板行为增加，这可能与皮质下端脑结构内DA活性的功能变化有关。这一发现可能表明额叶皮质内的DA在大鼠中具有行为抑制作用，尽管还需要进一步的研究来证实这一点。
