The orexin-1 receptor antagonist SB-334867 decreases sympathetic responses to a moderate dose of methamphetamine and stress.
The orexin-1 receptor antagonist SB-334867 decreases sympathetic responses to a moderate dose of methamphetamine and stress.
复制标题
orexin-1 受体拮抗剂 SB-334867 可降低对中等剂量甲基苯丙胺和压力的交感神经反应。
DOI：
10.1016/j.physbeh.2012.02.010
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发表时间：
2012
影响因子：
2.9
通讯作者：
DiMicco,JosephA
中科院分区：
文献类型：
--
作者：
Rusyniak,DanielE;Zaretsky,DmitryV;Zaretskaia,MariaV;Durant,PamelaJ;DiMicco,JosephA
我们最近发现，抑制下丘脑背内侧(DMH)的神经元可以减轻由取代的苯丙胺(MDMA)引起的体温升高、心动过速、高血压和多动。在DMH区域也发现了合成食欲素的神经元。由于食欲素及其受体参与心率和体温的调节，它们似乎是苯丙胺引起的效应的合理候选者。这项研究的目的是确定阻断清醒大鼠的食欲素-1受体是否会抑制由一定剂量的甲基苯丙胺引起的心血管和生热反应。雄性SD大鼠(每组6只)植入遥测发射器，测量体温、心率和平均动脉压。动物随机接受食欲素-1受体拮抗剂SB-334867(10 mg/kg)或等量赋形剂的预处理。30分钟后给动物腹腔注射(Ip)。注射生理盐水、低剂量(1 mg/kg)、中剂量(5 mg/kg)或高剂量(10 mg/kg)冰毒。SB-334867可显著降低中等剂量冰毒引起的体温和平均动脉压的升高，但不影响低剂量和高剂量冰毒引起的体温和平均动脉压的升高。此外，与赋形剂相比，使用SB-334867处理的动物在ip应激后体温和心率增加较低。注射。总而言之，温度和心血管对中等剂量冰毒和压力的反应似乎与食欲素-1受体有关。未能影响低剂量和高剂量的冰毒，表明存在依赖于剂量的复杂药理学。更好地理解这一点可能有助于了解单胺如何影响食欲素系统，反之亦然。
We recently discovered that inhibiting neurons in the dorsomedial hypothalamus (DMH) attenuated hyperthermia, tachycardia, hypertension, and hyperactivity evoked by the substituted amphetamine 3, 4-methylenedioxymethamphetamine (MDMA). Neurons that synthesize orexin are also found in the region of the DMH. As orexin and its receptors are involved in the regulation of heart rate and temperature, they would seem to be logical candidates as mediators of the effects evoked by amphetamines. The goal of this study was to determine if blockade of orexin-1 receptors in conscious rats would suppress cardiovascular and thermogenic responses evoked by a range of methamphetamine (METH) doses. Male Sprague–Dawley rats (n=6 per group) were implanted with telemetric transmitters measuring body temperature, heart rate, and mean arterial pressure. Animals were randomized to receive pretreatment with either the orexin-1 receptor antagonist SB-334867 (10mg/kg) or an equal volume of vehicle. Thirty minutes later animals were given intraperitoneal (i.p.) injections of either saline, a low (1mg/kg), moderate (5mg/kg) or high (10mg/kg) dose of METH. Pretreatment with SB-334867 significantly attenuated increases in body temperature and mean arterial pressure evoked by the moderate but not the low or high dose of METH. Furthermore, animals treated with SB-334867, compared to vehicle, had lower temperature and heart rate increases after the stress of an i.p. injection. In conclusion, temperature and cardiovascular responses to a moderate dose of METH and to stress appear to involve orexin-1 receptors. The failure to affect a low and a high dose of METH suggests a complex pharmacology dependent on dose. A better understanding of this may lead to the knowledge of how monoamines influence the orexin system and vice versa.