Yatham L N, Shiah I S, Lam R W, Tam E M, Zis A P
Department of Psychiatry, The University of British Columbia, Vancouver, Canada.
J Affect Disord. 1999 Aug;54(3):295-301. doi: 10.1016/s0165-0327(98)00186-4.
The selective 5-HT1A receptor agonist ipsapirone causes dose-dependent decrease in body temperature and increase in adrenocorticotropic hormone (ACTH) and cortisol release in humans. These responses are attenuated by 5-HT1A receptor antagonists, suggesting that hypothermia, ACTH and cortisol release induced by ipsapirone are indeed mediated by 5-HT1A receptors and that these responses provide a valid index of 5-HT1A receptor function in humans.
To examine the 5-HT1A receptor sensitivity in patients with mania, we studied six manic patients and six age and sex matched healthy controls. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained every 30 minutes for 3 hours.
We found that ACTH and cortisol responses to ipsapirone were significantly increased in mania when compared to healthy controls, but there was no significant difference in hypothermic response to ipsapirone between the two groups.
A lack of placebo control, heterogeneity of patients, and a small sample size are the limitations.
Our findings suggest that manic patients may have enhanced postsynaptic 5-HT1A receptor sensitivity, but presynaptic 5-HT1A receptors are unaltered in this condition. Further placebo-controlled studies with a larger number of manic patients are needed to verify this.
选择性5-羟色胺1A（5-HT1A）受体激动剂伊沙匹隆可使人体体温呈剂量依赖性下降，并使促肾上腺皮质激素（ACTH）和皮质醇释放增加。5-HT1A受体拮抗剂可减弱这些反应，这表明伊沙匹隆诱导的体温过低、ACTH和皮质醇释放确实是由5-HT1A受体介导的，并且这些反应为人类5-HT1A受体功能提供了一个有效的指标。
为了研究躁狂症患者的5-HT1A受体敏感性，我们对6名躁狂症患者和6名年龄及性别匹配的健康对照者进行了研究。在采集血样以测定基线激素水平并测量体温后，给所有受试者口服0.3mg/kg的伊沙匹隆单剂量，然后每30分钟采集一次血样并测量体温，持续3小时。
我们发现，与健康对照者相比，躁狂症患者对伊沙匹隆的ACTH和皮质醇反应显著增加，但两组对伊沙匹隆的体温过低反应没有显著差异。
缺乏安慰剂对照、患者的异质性以及样本量小是局限性所在。
我们的研究结果表明，躁狂症患者可能具有增强的突触后5-HT1A受体敏感性，但在此情况下突触前5-HT1A受体未发生改变。需要进一步对更多躁狂症患者进行安慰剂对照研究来验证这一点。
