Abstract：
Recent studies have shown that the 5-HT1a receptor (5-HT1aR) in the central 5-HT (Serotonergic) system is involved in the pathophysiology of schizophrenia through its various receptors, and the dysfunction of the ventral hippocampus may be a key causative factor in schizophrenia. To date, whether the 5-HT1a receptor is involved in ventral hippocampal dysfunction and its internal mechanism remain unclear. In this study, schizophrenia-like animal model was induced by intraperitoneal injection of aspartate receptor antagonist MK-801 in male Sprague Dawley rats, and the role of 5-HT1aR in this animal model was investigated by bilaterally micro-infusing the 5-HT1aR antagonist WAY100635 into the ventral subiculum (vSub) of the hippocampus of rats. Behavioral experiments such as open field test (OFT) and prepulse inhibition (PPI) were performed. The results showed that MK-801 induced hyperactivity and impaired prepulse inhibition in rats, whereas, micro-infusion of 5-HT1aR antagonist WAY100635 into the vSub ameliorated these phenomena. Immunofluorescence analysis revealed that WAY100635 significantly increased the c-Fos expression in vSub. Western blot and immunohistochemical analysis showed that MK-801 induced up-regulation of 5-HT1aR and phospho-extracellular regulated protein kinase (p-ERK) pathway, while micro-infusion of the WAY100635 down-regulated 5-HT1aR and p-ERK in the vSub. Therefore, the results of the present study suggested that in vSub, the 5-HT1aR antagonist WAY100635 may attenuate MK-801-induced schizophrenia-like activity by modulating excitatory neurons and downregulating p-ERK.
摘要：
最近的研究表明，中枢5-HT（血清素能）系统中的5-HT1a受体（5-HT1aR）通过其各种受体参与精神分裂症的病理生理，腹侧海马功能障碍可能是精神分裂症的关键致病因素。迄今为止,5-HT1a受体是否参与腹侧海马功能障碍及其内在机制尚不清楚.在这项研究中,通过腹腔注射天冬氨酸受体拮抗剂MK-801诱导雄性SD大鼠精神分裂症样动物模型,并通过将5-HT1aR拮抗剂WAY100635双侧微量输注到大鼠海马的腹下膜（vSub）中，研究了5-HT1aR在该动物模型中的作用。进行了行为实验，例如旷场测试（OFT）和预脉冲抑制（PPI）。结果表明，MK-801诱导大鼠多动症和前脉冲抑制受损，然而,将5-HT1aR拮抗剂WAY100635微输注到vSub中改善了这些现象。免疫荧光分析显示WAY100635显著增加vSub中的c-Fos表达。Westernblot和免疫组织化学结果显示MK-801诱导5-HT1aR和磷酸化细胞外调节蛋白激酶(p-ERK)通路上调,而WAY100635的微输注下调了vSub中的5-HT1aR和p-ERK。因此,本研究的结果表明，在vSub中，5-HT1aR拮抗剂WAY100635可能通过调节兴奋性神经元和下调p-ERK来减弱MK-801诱导的精神分裂症样活动。
