THE BASIC STUDIES ON THE PATHOGENESIS AND THE DIAGNOSIS OF BIPOLAR DISORDERS USING ^<31>P-MRS

虽然对情感性障碍患者5HT_2受体超敏的研究已有大量报道，但除了直接测定抑郁症患者血小板中5HT_2受体外，几乎没有发现。成像方式的最新进展彻底改变了我们了解体内受体和第二信使系统功能变化的能力。特别是，核磁共振波谱可以作为一种监测体内第二信使系统的工具。在这个项目中，我们首先研究了体内^<31>P-MRS是否可以检测肌醇-1-磷酸的积累。5HT_2激动剂（DOI）可增加PME水平，DOI刺激与未刺激的PME峰差异可归因于脑I-1-P水平的增加，但由于样本数量较少，尚未进行统计分析，无法得到确凿的数据。5HT_2拮抗剂（酮色林）预处理抑制了这种增加。其次，我们尝试制造5HT_2受体超敏大鼠。急性应激（固定应激1小时）和慢性应激（固定应激1小时）。/d，连续7 d)，比较5HT_2激动剂（DOI）的行为反应。慢性应激大鼠的摇头次数较未固定的对照组明显增加，认为慢性应激大鼠是5HT_2受体超敏感模型。第三，模型大鼠体内^<31>P-MRS检测PME/beta。由于实验还在继续，样本数量太少，无法进行统计分析，目前还无法得出结论。虽然需要进一步的实验来获得任何结论性的发现，但通过这个项目可以清楚地看到，一种监测PI周转率变化的非侵入性方法将有助于情感性障碍的研究。

Although a lot of investigations of 5HT_2 receptor supersensitivity in affective disorders have been reported, almost findings except the direct measurement of 5HT_2 receptors in platelets of depressed patients. Recent progress in imaging modalities revolutinalizes our capacity to understand the functional changes of receptors and the 2nd messenger system in vivo. Especially, NMR spectroscopy can be developed as a tool to monitor 2nd messenger system in vivo.In this project, firstly, we investigated whether the accumulation of inositol-1-phosphate can be detected by in vivo ^<31>P-MRS.5HT_2 agonist (DOI) was found to increase the level of PME and the difference of PME peak stimulated by DOI and not stimulated can be attributed to an increase in brain I-1-P levels, although we could not get conclusive data because the number of the samples was so small that the statistical analysis has not been done yet. This increase was suppressed by the pretreatment of 5HT_2 antagonist (ketanserin).Secondly, we tried to make the rats which showed 5HT_2 receptor supersensiivity. Acute stress (immobilization stress for 1 hr) and chronic stress (immobilization for 1 hr./day for 7 days) was administered to the rats and the behavioral reoponses to the 5HT_2 agonist (DOI) were compared. As the chronic stress rats showed significant increase of head shakes comparing with the non-immobilized controls, these rats were consdered to be the model of 5HT_2 recoptor supersensitivity.Thirdly, PME/beta was detected by in vivo ^<31>P-MRS in the model rats. We could not get the conclusion so far because the experiments are still continued and the number of the samples is too small to analyze statistically. Although further experiments should be done to obtain any conclusive findings, it became clear through this project that a non invasive methodology for monitoring changes in PI turnover would be helpful to the research of affective disorders.