Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: The TMN and VLPO as key elements in the pathway
Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: The TMN and VLPO as key elements in the pathway
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地尔硫卓对戊巴比妥诱导催眠的增强作用通过血清素能系统增强：TMN 和 VLPO 作为途径中的关键元件
DOI：
10.1016/j.neuropharm.2009.01.017
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发表时间：
2009-05
影响因子：
4.7
通讯作者：
Zhang, Yong-He
中科院分区：
文献类型：
--
作者：
Zhao, Xin;Cui, Xiang-Yu;Wang, Li-En;Zhang, Yong-He
为探讨L-型钙通道阻滞剂增强戊巴比妥钠催眠作用的机制，本研究观察了地尔硫卓（diltiazem）与多巴胺能神经系统的相互作用对戊巴比妥钠睡眠结构的影响，并检测了大鼠腹外侧视前核（VLPO）和结节乳头核（TMN）内c-Fos的表达。记录由EEG和EMG组成的多导睡眠图以分析睡眠结构。结果表明，地尔硫（2.0和5.0mg/kg，p.o.）增加总戊巴比妥睡眠和慢波睡眠（SWS），但减少快速眼动（REM）睡眠。5-羟色胺（5-HTP）是5-羟色胺的前体，可增强这些作用，但色氨酸羟化酶抑制剂对氯苯丙氨酸（PCPA）可消除这些作用。地尔硫卓（1 mg/kg，p.o.）或5-HTP（2mg/kg，i.p.）单独给药不改变戊巴比妥睡眠的结构和戊巴比妥诱导的VLPO和TMN中的c-Fos表达，但两者联合给药显著增加总戊巴比妥睡眠和SWS，而减少REM睡眠，增加VLPO中的c-Fos表达，同时减少TMN中的c-Fos表达。这些结果提示，地尔硫卓对戊巴比妥睡眠的增强作用可能与多巴胺能神经系统有关，VLPO-TMN神经回路可能起关键作用。
To investigate the mechanism by which L-type Ca2+channel blockers exerted potentiating effects on pentobarbital-induced hypnosis, the present study was undertaken to determine if the interaction of diltiazem and serotonergic system influences the architecture of pentobarbital sleep in rats and examined c-Fos expression in the ventrolateral preoptic nucleus (VLPO) and the tuberomammillary nucleus (TMN). The polysomnogram consisting of EEG and EMG was recorded for analyzing sleep architecture. The results showed that diltiazem (2.0 and 5.0 mg/kg, p.o.) increased both total pentobarbital sleep and slow wave sleep (SWS), but decreased rapid eye movement (REM) sleep. These effects were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, but abolished by p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Diltiazem (1 mg/kg, p.o.) or 5-HTP (2 mg/kg, i.p.) alone did not change the architecture of pentobarbital sleep and pentobarbital-induced c-Fos expression in the VLPO and the TMN, but co-administration of them significantly increased both total pentobarbital sleep and SWS, whereas decreased REM sleep, with increasing c-Fos expression in the VLPO and concomitantly decreasing c-Fos expression in the TMN. These findings indicate that the serotonergic system may be involved in the augmentative effect of diltiazem on pentobarbital sleep and the VLPO–TMN neuronal circuit may play a key role.
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DOI：
10.1073/pnas.95.13.7754
发表时间：
1998-06-23
影响因子：
11.1
作者：
Scammell, T;Gerashchenko, D;Hayaishi, O
通讯作者：
Hayaishi, O
影响因子：
4.7
作者：
S. Dolin;T. Patch;M. Rabbani;P. Taberner;H. Little
通讯作者：
S. Dolin;T. Patch;M. Rabbani;P. Taberner;H. Little
影响因子：
64.8
作者：
Gallopin, T;Fort, P;Serafin, M
通讯作者：
Serafin, M
影响因子：
56.9
作者：
Sherin, JE;Shiromani, PJ;Saper, CB
通讯作者：
Saper, CB
影响因子：
25
作者：
Cueni, Lucius;Canepari, Marco;Luthi, Anita
通讯作者：
Luthi, Anita