THE 5-HT1A RECEPTOR AGONIST, 8-OH-DPAT, PREFERENTIALLY ACTIVATES CELL BODY 5-HT AUTORECEPTORS IN RAT-BRAIN INVIVO
THE 5-HT1A RECEPTOR AGONIST, 8-OH-DPAT, PREFERENTIALLY ACTIVATES CELL BODY 5-HT AUTORECEPTORS IN RAT-BRAIN INVIVO
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DOI：
10.1007/bf00179315
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发表时间：
1988-11-01
影响因子：
3.6
通讯作者：
MAGNUSSON, T
中科院分区：
文献类型：
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作者：
HJORTH, S;MAGNUSSON, T
本研究旨在探讨5-HT 1A受体激动剂8-hydroxy-2-（di-n-propylamino）tetralin（8-OH-DPAT）对5-HT神经化学的影响是否通过5-HT自身受体介导。为此，我们确定了在中枢神经系统中的一些突出的5-HT神经元投射区域中的5-HT合成和释放/周转率的体内指数i）在对具有上升的中脑单胺神经元的急性单侧轴突切断术的大鼠全身施用8-OH-DPAT之后，或ii）在将化合物局部输注到完整大鼠的中缝背核（DRN）5-HT细胞体区域之后。横切不改变5-HT合成本身，但阻止合成抑制作用的8-OH-DPAT。因此，8-OH-DPAT的5-HT合成抑制作用高度依赖于中枢5-HT神经元中的完整脉冲流。另一方面，局部DRN应用化合物（1 μ g）导致在5-HT末端中测量的5-HT合成和释放指数的明显降低，例如，纹状体这些发现提供了直接的神经化学证据，通过优先刺激体树突5-HT 1A受体，8-OH-DPAT抑制5-HT神经元冲动流，从而实现减少终端5-HT的合成和释放。总之，数据与8-OH-DPAT优先在细胞体与末端5-HT自身受体中作为激动剂的建议一致，因此也强调了末端和细胞体5-HT自身受体之间的区别。所获得的结果可能有重要的影响，了解参与调节中枢胆碱能神经元的活动的机制。
The present study was undertaken in an attempt to assess whether the effects of the potent and selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, on cerebral 5-hydroxytryptamine (5-HT) neurochemistry in vivo are mediated via 5-HT autoreceptors on the cell bodies or on the terminals, and/or via postsynaptic 5-HT receptors. To this end we determined in vivo indices of 5-HT synthesis and release/turnover rates in a number of prominent 5-HT neuronal projection areas in the CNS i) after systemic administration of 8-OH-DPAT to rats with an acute unilateral axotomy of the ascending mesencephalic monoamine neurones, or ii) after local infusion of the compound into the dorsal raphe (DRN) 5-HT cell body region of intact rats. Transection did not alter 5-HT synthesis per se, but prevented the synthesis-inhibitory effect of 8-OH-DPAT. Thus, the 5-HT synthesis-inhibiting action of 8-OH-DPAT is highly dependent upon intact impulse flow in the central 5-HT neurones. On the other hand, local DRN application of the compound (1 .mu.g) resulted in a clearcut reduction of the 5-HT synthesis and release indices measured in 5-HT terminals in, e.g., the striatum. These findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5-HT neuronal impulse flow, thereby effectuating decreased terminal 5-HT synthesis and release. Taken together, the data are consistent with the suggestion that 8-OH-DPAT acts as an agonist preferentially at cell body vs. terminal 5-HT autoreceptors, therefore also emphasizing the distinction between terminal and cell body 5-HT autoreceptors. The results obtained may have important implications for the understanding of mechanisms involved in regulating the activity of central serotoninergic neurones.