Repeated treatment with antidepressants differentially alters 5-HT1A agonist-stimulated [35S]GTP gamma S binding in rat brain regions.
Repeated treatment with antidepressants differentially alters 5-HT1A agonist-stimulated [35S]GTP gamma S binding in rat brain regions.
复制标题
抗抑郁药的重复治疗会不同程度地改变大鼠大脑区域中 5-HT1A 激动剂刺激的 [35S]GTP gamma S 结合。
DOI：
10.1016/s0028-3908(02)00064-3
复制
发表时间：
2002
影响因子：
4.7
通讯作者：
Meller,E
中科院分区：
文献类型：
--
作者：
Shen,C;Li,H;Meller,E
电生理学研究表明，药物治疗焦虑和抑郁的神经生物学机制涉及5-HT 1A受体敏感性的区域特异性适应。根据所使用的药物，在治疗数周后，抑制性体树突自身受体的敏感性降低，突触后受体的敏感性增加，或两者都发生改变。用放射自显影法测定N，N-二丙基-5-羧酰胺色胺刺激的鸟苷-5 ′-O-（3-硫代）三磷酸（[35 S]GTPγS）结合来验证这一假设。用四种不同的抗焦虑/抗抑郁药物（mg/kg）中的一种治疗大鼠21天：氟西汀（10），丙咪嗪（10），氯吉兰（1），伊沙匹隆（2×20）或生理盐水。研究了3个富含5-HT 1A受体的脑区：中缝背核（体树突）、背侧海马（突触后）和侧隔（突触后）。只有丙咪嗪（+17%）和氟西汀（+54%）显著增加了背侧海马中激动剂刺激的结合;除丙咪嗪外，所有药物均显著降低了中缝背侧的结合（-19至-41%）。这些结果通常支持通过一种或多种5-HT受体亚型净增强海马5-HT神经传递的概念。然而，最一致的效果是在所有四种治疗后，外侧隔中刺激的[35 S]GTPγS结合显著降低（−14至−23%），这表明这可能是迄今为止未被认识到的抗抑郁治疗的共同结果，值得进一步研究。
Electrophysiological studies have led to the proposal that the neurobiological mechanism(s) underlying drug therapy of anxiety and depression involve(s) regionally specific adaptations in 5-HT1Areceptor sensitivity. Depending on the drug utilized, a decrease in sensitivity of inhibitory somatodendritic autoreceptors, an increase in sensitivity of postsynaptic receptors, or both alterations, occur after several weeks of treatment. This hypothesis was tested using N,N-dipropyl-5-carboxamidotryptamine-stimulated guanosine-5′-O-(3-thio)triphosphate ([35S]GTPγS) binding assessed by autoradiography. Rats were treated for 21 days with one of four different anxiolytic/antidepressant drugs (in mg/kg): fluoxetine (10), imipramine (10), clorgyline (1), ipsapirone (2×20) or saline. Three brain regions rich in 5-HT1Areceptors were examined: the dorsal raphe (somatodendritic), the dorsal hippocampus (postsynaptic) and the lateral septum (postsynaptic). Only imipramine (+17%) and fluoxetine (+54%) significantly increased agonist-stimulated binding in the dorsal hippocampus; all drugs except imipramine significantly decreased binding in the dorsal raphe (−19 to −41%). These results generally support the concept of a net enhancement of hippocampal 5-HT neurotransmission via one or more 5-HT receptor subtypes. The most consistent effect, however, was a significant decrease in stimulated [35S]GTPγS binding in the lateral septum after all four treatments (−14 to −23%), suggesting that this may be a heretofore unrecognized common outcome of antidepressant treatment deserving further study.