Mechanism of triazolo-benzodiazepine and benzodiazepine action in anxiety and depression: behavioral studies with concomitant in vivo CA1 hippocampal norepinephrine and serotonin release detection in the behaving animal.

Mechanism of triazolo-benzodiazepine and benzodiazepine action in anxiety and depression: behavioral studies with concomitant in vivo CA1 hippocampal norepinephrine and serotonin release detection in the behaving animal.
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三唑并苯二氮卓类药物和苯二氮卓类药物在焦虑和抑郁中的作用机制:行为动物体内 CA1 海马去甲肾上腺素和血清素释放检测的行为研究。

DOI:
10.1016/s0278-5846(98)00010-4
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发表时间:
1998
影响因子:
5.6
通讯作者:
Jeannot,P
Jeannot,P
中科院分区:
医学2区
文献类型:
--
作者:
Broderick,PA;Hope,O;Jeannot,P

文献摘要

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1.1.使用微型碳基传感器进行实时体内微伏安研究,同时检测自由运动和行为的雄性Sprague Dawley实验室大鼠海马ca1区2个不同电化学信号中去甲肾上腺素(NE)和血清素(5-HT)的释放。同时,采用红外光束检测方法检测小鼠的4个野外行为参数,即行走、饲养、精细运动和中央行走行为(焦虑减少行为的衡量指标)。时间过程研究表明,三唑苯二氮卓(TBZD)、adinazolam (Deracyn®)的作用机制与经典苯二氮卓(BZD)、地西泮(Valium®)的作用机制显著不同,即adinazolam增加,而diazepam减少,自由活动和行为大鼠海马ca1区5-HT释放。安地唑仑使自由活动和行为大鼠海马ca1区NE释放先增加后降低,而地西泮仅降低NE的电化学信号;阿地唑仑产生的NE减少量大于地西泮释放的NE减少量。同样的动物对照的行为活动模式,同时检测NE释放和5-羟色胺释放的体内微伏安信号,表明BZD,即地西泮,比TBZD adinazolam表现出更有效的镇静特性。伴随行为效应的TBZD、adinazolam海马5-HT和NE释放效应解释了TBZD的双重抗焦虑/抗抑郁特性。
1.1.Real time, in vivomicrovoltammetric studies were performed, using miniature carbon-based sensors, to concurrently detect norepinephrine (NE) release and serotonin (5-HT) release, in 2 separate electrochemical signals, within CA1region of hippocampus in the freely moving and behaving, male, Sprague Dawley laboratory rat.2.2. Concurrently, four parameters of open-field Behavior I.E. Ambulations, Rearing, Fine Movements and Central Ambulatory behavior (a measure of anxiety reduction behavior), were assayed by infrared photobeam detection.3.3. Time course studies showed that the mechanism of action of the triazolobenzodiazepine (TBZD), adinazolam, (Deracyn®) is dramatically different from that of the classical benzodiazepine (BZD), diazepam (Valium®) i.e., adinazolam increased, whereas diazepam decreased, 5-HT release within CA1region of hippocampus in the freely moving and behaving rat.4.4. Adinazolam initially increased NE release and then decreased NE release in CA1region of hippocampus in the freely moving and behaving rat whereas diazepam only decreased the electrochemical signal for NE; the decrease in NE produced by adinazolam was greater than the decrease in NE release produced by diazepam.5.5. The Behavioral Activity Patterns, derived from same animal controls, simultaneously with detection ofin vivomicrovoltammetric signals for NE release and 5-HT release, showed that the BZD, diazepam, exhibited more potent sedative properties than did the TBZD adinazolam.6.6. Hippocampal 5-HT and NE release effects of the TBZD, adinazolam, concomitant with behavioral effects lends explanation to the dual anxiolytic/antidepressant properties of the TBZDs.