Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
Neuroscience. 2010 Aug 11;169(1):132-42. doi: 10.1016/j.neuroscience.2010.04.076. Epub 2010 May 6.
Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes has been used to demonstrate that sub-second changes in catecholamine concentration occur within the nucleus accumbens (NAc) shell during motivated behaviors, and these fluctuations have been attributed to rapid dopamine signaling. However, FSCV cannot distinguish between dopamine and norepinephrine, and caudal regions of the NAc shell receive noradrenergic projections. Therefore, in the present study, we examined the degree to which norepinephrine contributes to catecholamine release within rostral and caudal portion of NAc shell. Analysis of tissue content revealed that dopamine was the major catecholamine detectable in the rostral NAc shell, whereas both dopamine and norepinephrine were found in the caudal subregion. To examine releasable catecholamines, electrical stimulation was used to evoke release in anesthetized rats with either stimulation of the medial forebrain bundle, a pathway containing both dopaminergic and noradrenergic projections to the NAc, or the ventral tegmental area/substantia nigra, the origin of dopaminergic projections. The catecholamines were distinguished by their responses to different pharmacological agents. The dopamine autoreceptor blocker, raclopride, as well as the monoamine and dopamine transporter blockers, cocaine and GBR 12909, increased evoked catecholamine overflow in both the rostral and caudal NAc shell. The norepinephrine autoreceptor blocker, yohimbine, and the norepinephrine transporter blocker, desipramine, increased catecholamine overflow in the caudal NAc shell without significant alteration of evoked responses in the rostral NAc shell. Thus, the neurochemical and pharmacological results show that norepinephrine signaling is restricted to caudal portions of the NAc shell. Following raclopride and cocaine or raclopride and GBR 12909, robust catecholamine transients were observed within the rostral shell but these were far less apparent in the caudal NAc shell, and they did not occur following yohimbine and desipramine. Taken together, the data demonstrate that catecholamine signals in the rostral NAc shell detected by FSCV are due to change in dopamine transmission.
在碳纤维微电极上进行快速扫描循环伏安法(FSCV)已被用于证明,在动机行为期间,壳核 accumbens(NAc)内的儿茶酚胺浓度会发生亚秒级的变化,并且这些波动归因于快速多巴胺信号传递。然而,FSCV 无法区分多巴胺和去甲肾上腺素,而 NAc 壳的尾部区域接收去甲肾上腺素投射。因此,在本研究中,我们检查了去甲肾上腺素在 NAc 壳的头尾部区域对儿茶酚胺释放的贡献程度。组织含量分析表明,在 NAc 壳的头端可检测到多巴胺是主要的儿茶酚胺,而在尾部区域则可检测到多巴胺和去甲肾上腺素。为了检查可释放的儿茶酚胺,使用电刺激在麻醉大鼠中引发释放,刺激内侧前脑束,该通路包含向 NAc 的多巴胺能和去甲肾上腺素能投射,或腹侧被盖区/黑质,多巴胺能投射的起源。儿茶酚胺通过其对不同药理学药物的反应来区分。多巴胺自受体阻断剂,raclopride,以及单胺和多巴胺转运体阻断剂,可卡因和 GBR 12909,增加了 NAc 壳的头端和尾部的诱发儿茶酚胺溢出。去甲肾上腺素自受体阻断剂,育亨宾,和去甲肾上腺素转运体阻断剂,去甲丙咪嗪,增加了 NAc 壳的尾部的儿茶酚胺溢出,而对 NAc 壳的头端的诱发反应没有显著改变。因此,神经化学和药理学结果表明,去甲肾上腺素信号仅限于 NAc 壳的尾部。在给予 raclopride 和 cocaine 或 raclopride 和 GBR 12909 之后,在 NAc 壳的头端观察到强烈的儿茶酚胺瞬变,但在 NAc 壳的尾部则不太明显,并且在给予育亨宾和去甲丙咪嗪后则没有观察到。总之,这些数据表明,FSCV 检测到的 NAc 壳的头端儿茶酚胺信号归因于多巴胺传递的变化。