Hui Y P, Zhang Q J, Zhang L, Chen L, Guo Y, Qiao H F, Wang Y, Liu J
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
Neuroscience. 2014 May 30;268:265-75. doi: 10.1016/j.neuroscience.2014.03.033. Epub 2014 Mar 26.
Depression is a common symptom in Parkinson's disease (PD), but its pathophysiology remains unclear. Several lines of studies have revealed that the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex and 5-HT1A receptors are involved in the regulation of depression. In this study, we examined whether complete unilateral lesions of the medial forebrain bundle (MFB) using 6-hydroxydopamine in rats are able to induce depressive-like behaviors, the role of PrL 5-HT1A receptors in the regulation of these behaviors, and co-localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1-ir) neurons in the PrL. The MFB lesions induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. The intra-PrL injection of 5HT1A receptor agonist 8-OH-DPAT (50, 100, and 500ng/rat) increased sucrose consumption, and decreased immobility time in both sham-operated and the lesioned rats, indicating the induction of antidepressant effects. Furthermore, the intra-PrL injection of 5HT1A receptor antagonist WAY-100635 (60, 120, and 240ng/rat) showed a decrease in sucrose consumption, and an increase in immobility time, indicating the induction of depressive-like responses. However, the effective doses in the lesioned rats were higher than those in sham-operated rats, which attribute to down-regulation of 5-HT1A receptor expression on EAAC1-ir neurons in the PrL of the lesioned rats. These findings suggest that unilateral lesions of the MFB in rats may induce depressive-like behaviors, and 5-HT1A receptors of the PrL play an important role in the regulation of these behaviors.
抑郁症是帕金森病（PD）的常见症状，但其病理生理学仍不清楚。多项研究表明，腹内侧前额叶皮质的前边缘（PrL）亚区和5-HT1A受体参与了抑郁症的调节。在本研究中，我们检测了使用6-羟基多巴胺对大鼠内侧前脑束（MFB）进行完全单侧损伤是否能够诱导出抑郁样行为、PrL 5-HT1A受体在这些行为调节中的作用，以及PrL中5-HT1A受体与神经元谷氨酸转运体EAAC1免疫反应性（EAAC1-ir）神经元的共定位情况。与假手术大鼠相比，通过蔗糖偏好试验和强迫游泳试验测量发现，MFB损伤诱导了抑郁样反应。向PrL内注射5HT1A受体激动剂8-OH-DPAT（50、100和500 ng/大鼠）可增加假手术大鼠和损伤大鼠的蔗糖消耗量，并减少不动时间，表明诱导了抗抑郁作用。此外，向PrL内注射5HT1A受体拮抗剂WAY-100635（60、120和240 ng/大鼠）可导致蔗糖消耗量减少，不动时间增加，表明诱导了抑郁样反应。然而，损伤大鼠的有效剂量高于假手术大鼠，这归因于损伤大鼠PrL中EAAC1-ir神经元上5-HT1A受体表达的下调。这些发现表明，大鼠MFB的单侧损伤可能诱导抑郁样行为，PrL的5-HT1A受体在这些行为的调节中起重要作用。
