Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test.
Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel conflict test.
复制标题
沃格尔冲突试验中坦度螺酮抗焦虑作用的血清素机制。
DOI：
10.1254/jjp.59.105
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
M. Nakamura
中科院分区：
文献类型：
--
作者：
H. Shimizu;T. Tatsuno;H. Tanaka;A. Hirose;Y. Araki;M. Nakamura
为了阐明哪种5-HT 1A受体（位于中缝核的自身受体或接受5-HT输入的前脑区域的突触后受体）介导坦度螺酮（一种5-HT 1A受体相关的抗焦虑药）的抗冲突作用，在5，7-二羟色胺（5，7-DHT）处理的大鼠中研究了坦度螺酮的行为效应。通过测定5，7-DHT处理的大鼠脑内单胺及其代谢产物的水平和[3 H]8-OH-DPAT结合密度，我们证实了5，7-DHT预处理选择性地破坏5-HT神经元，而不影响位于突触后神经元上的5-HT 1A受体。这种选择性破坏对大鼠的饮酒行为没有产生显著的影响，无论是在沃格尔冲突测试的惩罚还是未惩罚阶段。此外，这种破坏既不改变坦度螺酮在该过程中对惩罚性反应的影响，也不改变坦度螺酮诱导大鼠平坦身体姿势的效力，这被称为“5-羟色胺行为综合征”。这些结果表明，坦度螺酮的抗冲突作用可能产生，至少部分，通过结合突触后5-HT 1A受体，并激活它们作为激动剂，而不是5-HT 1A自身受体位于5-HT神经元的细胞体。
To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics), the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This selective destruction produced no significant changes in the drinking behavior of rats in either punished or unpunished sessions of the Vogel conflict test. Furthermore, this destruction altered neither the effect of tandospirone on punished responding in this procedure nor the potency of tandospirone to induce a flat body posture in rats, which is known as the "serotonin behavioral syndrome". These results suggested that the anticonflict action of tandospirone may be produced, at least in part, by binding to postsynaptic 5-HT1A receptors and activating them as agonists, and not to 5-HT1A autoreceptors located on the cell bodies of 5-HT neurons.