边缘前皮质α1受体调节帕金森病焦虑模型大鼠杏仁核的活动
Prelimbic α1-Adrenoceptors are involved in regulation of neural activities in the amygdala in a rat model of Parkinson’s disease with anxiety

摘要：目的 观察激活或阻断边缘前皮质(prelimbic cortex, PrL)内α1肾上腺素受体(α1受体)对帕金森病(Parkinson’s disease, PD)模型大鼠焦虑样行为和杏仁核神经活动的影响。 方法 采用6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)单侧损毁内侧前脑束(medial forebrain bundle, MFB)法建立PD大鼠模型，旷场实验检测大鼠的焦虑样行为；通过导向套管向PrL内注射α1受体激动剂或拮抗剂后检测对大鼠焦虑样行为、杏仁核中单胺类递质含量以及c-Fos表达变化的影响。结果 6-OHDA单侧损毁MFB的PD模型大鼠产生焦虑样行为(P<0.001)。激活PrL内α1受体可诱导或增强大鼠的焦虑样行为(假手术组P<0.001；损毁组P<0.05)，而阻断α1受体则产生了抗焦虑样效应(假手术组P<0.001；损毁组P<0.05)。在假手术组，激活大鼠PrL内α1受体增加杏仁核多巴胺(DA)和5-羟色胺(5-HT)水平(P均<0.001)，而阻断α1受体则降低杏仁核内DA和5-HT水平(P均<0.001)。在损毁组，激活大鼠PrL内α1受体增加杏仁核内NA(P<0.01)和5-HT水平(P<0.001)，而阻断α1受体则降低杏仁核内NA和5-HT水平(P均<0.001)。大鼠PrL内局部注射α1受体激动剂后杏仁核中c-Fos表达阳性神经元的平均密度显著增加(假手术组、损毁组：P<0.001)。结论 激活或阻断PrL内α1受体改变了杏仁核的神经活动，参与调节PD大鼠焦虑样行为。
ABSTRACT: Objective To observe the effects of activation or blockade of the prelimbic (PrL) α1-adrenoceptors on anxiety-like behaviors and amygdaloid neural activities in rats with Parkinson’s disease (PD). Methods The rat model of PD was established by 6-hydroxydopamine (6-OHDA) unilateral lesion of the medial forebrain bundle (MFB). Then the anxiety-like behavior of rats was detected by the open field test. In addition, the changes of anxiety-like behavior, the effects of PrL α1-adrenoceptor stimulation on monoamines and c-Fos expression in the amygdala were also observed after local injection of the selective α1-adrenoceptor agonist or antagonist into the PrL by guided cannula. Results Unilateral 6-OHDA lesions of the MFB in rats induced anxiety-like behaviors (P<0.001). Furthermore, activation of the PrL α1-adrenoceptors significantly induced or enhanced anxiety-like behaviors in the rats (sham group: P<0.001; lesion group: P<0.05), while blockade of the α1-adrenoceptors produced anxiolytic effects (sham group: P<0.001; lesion group: P<0.05). Then activation of the PrL α？？1-adrenoceptors increased the levels of DA and 5-HT while blockade of the PrL α1-adrenoceptors decreased DA and 5-HT levels in the amygdala in sham-operated rats (DA & 5-HT: P<0.001). However, compared to those of sham-operated rats, activation of the PrL α1-adrenoceptors increased the levels of NA and 5-HT while blockade of the PrL α1-adrenoceptors decreased NA and 5-HT levels in the amygdala in the lesioned rats (NA & 5-HT: P<0.001) . In addition, the density of c-Fos immunoreactive positive neurons in the amygdala increased after intra-PrL injection α1-adrenoceptors agonist phenylephrine (sham group & lesion group: P<0.001). Conclusion These findings indicate that changed neural activities in the amygdala after activation or blockade of the PrL α1-adrenoceptors are involved in regulating anxiety-like