Department of Radiology, Keck School of Medicine of USC, Second Floor Imaging, Los Angeles, California 90033, USA.
Synapse. 2012 Mar;66(3):220-31. doi: 10.1002/syn.21503. Epub 2011 Nov 28.
Nitric oxide (NO) is a gaseous neurotransmitter synthesized in the nucleus accumbens (NAc) by aspiny interneurons containing neuronal NO synthase (nNOS). nNOS activity is readily assayed using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining and is believed to be regulated by activation of dopamine (DA) D1- and D2-like receptors. However, the role of DA transmission in the regulation of nNOS activity in identified subregions of the NAc remains unexplored. In this study, the impact of pharmacological manipulations of D1, D2, and NMDA receptors on nNOS activity was determined using optical density measures of NADPH-d staining preformed in multiple subdivisions (core, medial shell, intermediate shell, and lateral shell) of the NAc. Awake behaving rats received systemic administration of vehicle and/or the following drugs ~25 min prior to tissue harvesting: the nNOS inhibitor N(G) -propyl-L-arginine (NPA), the D1 receptor agonist SKF 81297, the D1 receptor antagonist SCH 23390, the D2 receptor agonist quinpirole (QNP), the D2 receptor antagonist eticlopride (ETI), or the NMDA receptor antagonist 3-((±)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). In vehicle-treated animals, a distinct medial-lateral histochemical gradient of NADPH-d staining was observed, which was characterized by moderate staining in the core and medial shell and more robust staining in the intermediate and lateral shell. Administration of NPA, SCH 23390, QNP, and CPP attenuated staining preferentially in the intermediate and lateral shell. SKF 81297 and ETI administration consistently increased staining in the medial shell in a manner, which was attenuated following pretreatment with SCH 23390, QNP, NPA, and CPP. These observations demonstrate that nNOS activity measured in distinct subregions of the NAc is differentially modulated by DA D1 and D2 receptor activation. Moreover, these findings demonstrate for the first time that DA D1 and D2 receptor activation regulates the facilitatory influence of glutamatergic transmission on nNOS activity in the NAc medial shell via facilitation (D1) or suppression (D2) of NMDA receptor function.
一氧化氮（NO）是一种气体神经递质，由含有神经元型一氧化氮合酶（nNOS）的棘突间神经元在伏隔核（NAc）中合成。nNOS 活性可以通过烟酰胺腺嘌呤二核苷酸磷酸-黄递酶（NADPH-d）染色来轻松检测，并且据信受多巴胺（DA）D1 和 D2 样受体激活的调节。然而，DA 传递在调节 NAc 中鉴定的亚区中的 nNOS 活性中的作用仍未得到探索。在这项研究中，使用 NADPH-d 染色的光密度测量值，在 NAc 的多个细分（核心、内侧壳、中间壳和外侧壳）中确定了 D1、D2 和 NMDA 受体的药理学操作对 nNOS 活性的影响。在组织收获前约 25 分钟，清醒的行为大鼠接受了载体和/或以下药物的全身给药：nNOS 抑制剂 N(G)-丙基-L-精氨酸（NPA）、D1 受体激动剂 SKF 81297、D1 受体拮抗剂 SCH 23390、D2 受体激动剂喹吡罗（QNP）、D2 受体拮抗剂 eticlopride（ETI）或 NMDA 受体拮抗剂 3-((±)2-羧基哌嗪-4-基)丙基-1-膦酸（CPP）。在载体处理的动物中，观察到 NADPH-d 染色的明显的内侧-外侧组织化学梯度，其特征在于核心和内侧壳中的中等染色和中间和外侧壳中的更强烈的染色。NPA、SCH 23390、QNP 和 CPP 的给药优先减弱了中间和外侧壳中的染色。SKF 81297 和 ETI 的给药一致地增加了内侧壳中的染色，这种增加在预先用 SCH 23390、QNP、NPA 和 CPP 预处理后减弱。这些观察结果表明，NAc 不同亚区中测量的 nNOS 活性受 DA D1 和 D2 受体激活的差异调节。此外，这些发现首次表明，DA D1 和 D2 受体激活通过促进（D1）或抑制（D2）NMDA 受体功能来调节谷氨酸能传递对 NAc 内侧壳中 nNOS 活性的促进作用。
