Sun Yi-Na, Wang Tao, Wang Yong, Han Ling-Na, Li Li-Bo, Zhang Yu-Ming, Liu Jian
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Neuropharmacology. 2015 Aug;95:181-91. doi: 10.1016/j.neuropharm.2015.03.007. Epub 2015 Mar 19.
Although the medial subdivision of the central nucleus of the amygdala (CeM) and serotonin-1A (5-HT1A) receptors are involved in the regulation of anxiety, their roles in Parkinson's disease (PD)-associated anxiety are still unknown. Here we assessed the importance of CeM 5-HT1A receptors for anxiety in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). The lesion induced anxiety-like behaviors, increased the firing rate and burst-firing pattern of CeM γ-aminobutyric acid (GABA) neurons, as well as decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip). Intra-CeM injection of the selective 5-HT1A receptor agonist 8-OH-DPAT produced anxiolytic effects in the lesioned rats, and decreased the firing rate of CeM GABAergic neurons in two groups of rats. Compared to sham-operated rats, the duration of the inhibitory effect on the firing rate of GABAergic neurons was shortened in the lesioned rats. The injection increased DA levels in the mPFC and amygdala in two groups of rats and the vHip in the lesioned rats, and increased 5-HT level in the lesioned rats, whereas it decreased NA levels in the mPFC in two groups of rats and the vHip in the lesioned rats. Moreover, the mean density of 5-HT1A receptor and GABA double-labeled neurons in the CeM was reduced after the lesioning. These results suggest that activation of CeM 5-HT1A receptor produces anxiolytic effects in the 6-OHDA-lesioned rats, which involves decreased firing rate of the GABAergic neurons, and changed monoamine levels in the limbic and limbic-related brain regions.
尽管杏仁核中央核内侧亚区（CeM）和5-羟色胺1A（5-HT1A）受体参与焦虑调节，但其在帕金森病（PD）相关焦虑中的作用仍不清楚。在此，我们评估了CeM 5-HT1A受体对单侧中脑前脑束（MFB）6-羟基多巴胺（6-OHDA）损伤大鼠焦虑的重要性。该损伤诱发了焦虑样行为，增加了CeMγ-氨基丁酸（GABA）能神经元的放电频率和爆发式放电模式，同时降低了纹状体、内侧前额叶皮质（mPFC）、杏仁核和海马腹侧部（vHip）中的多巴胺（DA）水平。向CeM内注射选择性5-HT1A受体激动剂8-OH-DPAT对损伤大鼠产生抗焦虑作用，并降低了两组大鼠CeM GABA能神经元的放电频率。与假手术大鼠相比，损伤大鼠中对GABA能神经元放电频率的抑制作用持续时间缩短。该注射增加了两组大鼠mPFC和杏仁核以及损伤大鼠vHip中的DA水平，并增加了损伤大鼠中的5-羟色胺（5-HT）水平，而降低了两组大鼠mPFC和损伤大鼠vHip中的去甲肾上腺素（NA）水平。此外，损伤后CeM中5-HT1A受体与GABA双标神经元的平均密度降低。这些结果表明，激活CeM 5-HT1A受体对6-OHDA损伤大鼠产生抗焦虑作用，这涉及GABA能神经元放电频率降低以及边缘和边缘相关脑区单胺水平的改变。
