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

尽管对情感性精神障碍的5-HT_2受体超敏性的研究已有很多报道，但除直接测定抑郁症患者血小板5-HT_2受体外，其余均未见报道。近年来影像学的发展使我们对受体和第二信使系统在体内功能变化的认识发生了革命性的变化。在本课题中，我们首先研究了在体脑内1-磷酸肌醇（inositol-1-phosphate，IP-P）的积累，发现5 <31>HT_2激动剂（DOI）可增加PME的水平，DOI刺激前后PME峰的差异可能与脑内I-1-P水平的增加有关，虽然由于样本数目太少，尚未进行统计分析，因此未能得出结论性数据。用5HT_2受体拮抗剂酮色林预处理可抑制这种增加。急性应激（制动应激1小时）和慢性应激（制动应激1小时）。连续7天），比较5-HT_2激动剂（DOI）对大鼠行为学的影响。由于慢性应激组大鼠的摇头次数较非制动对照组明显增加，故认为该模型为5HT_2受体超敏感性模型<31>。由于实验仍在进行中，样本数量太少，无法进行统计分析，目前还不能得出结论。虽然进一步的实验应该做，以获得任何结论性的发现，它变得很清楚，通过这个项目，一个非侵入性的方法来监测PI营业额的变化将有助于情感障碍的研究。

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.