Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Brain Res. 2011 Jan 12;1368:52-8. doi: 10.1016/j.brainres.2010.10.029. Epub 2010 Oct 19.
Local perfusion of morphine produces increased levels of extracellular ascorbic acid (AA) in the nucleus accumbens (NAc) of freely moving rats. However, the pathways that regulate morphine-induced AA release in the NAc are unclear. In the present study, we used high performance liquid chromatography with electrochemical detection (HPLC-ECD) to examine the effects of intra-ventral tegmental area (VTA) administration of a GABA(A) agonist and antagonist on morphine-induced increases in AA of the NAc. Also, using high performance liquid chromatography with fluorescent detection (HPLC-FD) and HPLC-ECD, the releases of γ-aminobutyric acid (GABA) and dopamine (DA) in the NAc induced by intra-VTA administration of a GABA(A) agonist and antagonist were also investigated. The results obtained showed that morphine (1 mM), locally perfused into the NAc, significantly increased AA release in the NAc and also GABA release. Intra-VTA infusion of bicuculline (150 ng/rat), a GABA receptor antagonist, not only abolished the enhanced extracellular AA and GABA levels produced by local perfusion of morphine but also decreased the basal release of extracellular GABA and increased the basal release of extracellular DA in the NAc. Muscimol (100 ng/rat), a GABA receptor agonist, affected the basal release of GABA and DA, but not the basal AA levels, or the morphine-induced changes in AA and GABA levels. These findings suggest that the GABA(A) receptors in the VTA play an important role in the modulation of morphine-induced AA release in the NAc, and the effect of morphine on AA release in the NAc is partially regulated by the GABA(A) receptor-mediated action of DA afferents from the VTA.
局部灌注吗啡可使自由活动大鼠伏隔核（NAc）细胞外抗坏血酸（AA）水平升高。然而，调节吗啡诱导的 NAc 中 AA 释放的途径尚不清楚。在本研究中，我们使用高效液相色谱电化学检测法（HPLC-ECD）检查腹侧被盖区（VTA）内给予 GABA（A）激动剂和拮抗剂对吗啡诱导的 NAc 中 AA 增加的影响。此外，使用高效液相色谱荧光检测法（HPLC-FD）和 HPLC-ECD，还研究了 VTA 内给予 GABA（A）激动剂和拮抗剂对内 VTA 给药诱导的 NAc 中γ-氨基丁酸（GABA）和多巴胺（DA）的释放。结果表明，吗啡（1mM）局部灌注到 NAc 中，可显著增加 NAc 中的 AA 释放，并增加 GABA 释放。VTA 内输注 GABA 受体拮抗剂荷包牡丹碱（150ng/大鼠）不仅消除了局部灌注吗啡产生的增强的细胞外 AA 和 GABA 水平，而且还降低了 NAc 中细胞外 GABA 的基础释放，并增加了细胞外 DA 的基础释放。GABA 受体激动剂 muscimol（100ng/大鼠）影响 GABA 和 DA 的基础释放，但不影响基础 AA 水平，或吗啡诱导的 AA 和 GABA 水平变化。这些发现表明，VTA 中的 GABA（A）受体在调节吗啡诱导的 NAc 中 AA 释放中起重要作用，而吗啡对 NAc 中 AA 释放的影响部分受 VTA 中 DA 传入的 GABA（A）受体介导的作用调节。
