Antisense confirmation of mu- and kappa-opioid receptor mediation of morphine's effects on body temperature in rats
Antisense confirmation of mu- and kappa-opioid receptor mediation of morphine's effects on body temperature in rats
复制标题
DOI：
10.1016/s0376-8716(96)01295-1
复制
发表时间：
1996-12-11
影响因子：
4.2
通讯作者：
Adler, MW
中科院分区：
文献类型：
--
作者：
Chen, XH;Geller, EB;Adler, MW
以前的研究表明，静脉注射4-16 mg/kg的吗啡可显著提高大鼠的体温，但更高剂量的吗啡(皮下注射大于或等于30 mg/kg)则使体温显著下降。基于选择性阿片激动剂和拮抗剂的使用，我们推测这些作用分别是由于吗啡对Mu和kappa受体的作用。在目前的研究中，我们试图确定针对克隆的u或kappa阿片受体的反义寡核苷酸(AS)是否会影响吗啡诱导的体温变化。AS寡核苷酸针对Mu受体编码区的1-18核苷酸和IC受体编码区的4-21核苷酸。雄性SD大鼠经外科手术植入脑室(ICON)套管。分别于第1、3、5天在动物集落室内冰冻注射溶剂或寡核苷酸。向自由活动动物注入L 30只以上体积5亩的寡核苷酸或错义寡核苷酸。在第6天，对大鼠进行测试。结果表明，冰冻治疗时，使用抗Mu阿片受体的AS寡核苷酸，而不是抗Mu阿片受体的MS寡核苷酸或抗kappa阿片受体的AS寡核苷酸，可以显著减轻通常由相对较低剂量的吗啡sc引起的体温升高。此外，使用抗kappa受体的AS寡核苷酸，而不是抗Re阿片受体的MS寡核苷酸或抗Mu阿片受体的AS寡核苷酸，可显著阻断高剂量吗啡引起的体温降低。这项研究证实了我们早先的假设，即sc 4 mg/kg的吗啡主要通过大脑中的u阿片受体引起体温升高，而大剂量(30 mg/kg)的吗啡sc主要通过大脑中的kappa阿片受体引起体温下降。
Previous studies showed that parenterally administered morphine at 4-16 mg/kg markedly increased body temperature in the rat, but higher doses of morphine (greater than or equal to 30 mg/kg, subcutaneously, sc) caused a profound decrease in body temperature. Based on the use of selective opioid agonists and antagonists, we postulated that these effects were due to morphine's actions on mu and kappa receptors, respectively. In the present study, we sought to determine whether an antisense (AS) oligodeoxynucleotide (oligo) against cloned mu or kappa opioid receptors could affect morphine-induced body temperature changes. AS oligos were directed against nucleotides 1-18 of the coding region of the mu receptor and 4-21 of the coding region of the Ic receptor. Male SD rats were surgically implanted with intracerebroventricular (icy) cannulae. Rats received icy injections of vehicle or oligo in the animal colony room on days 1, 3 and 5. Either AS oligo or missense (MS) oligo was infused in a volume of 5 mu l over 30 s to freely moving animals. On day 6, the rats were tested. The results showed that icy treatment with an AS oligo against mu opioid receptors, but not an MS oligo against the mu opioid receptor or an AS oligo against the kappa opioid receptor, significantly attenuated the hyperthermia normally produced by a relatively low dose of morphine administered sc. In addition, treatment with an AS oligo against kappa receptors, but not an MS oligo against re opioid receptor or an AS oligo against the mu opioid receptor, significantly blocked the hypothermia induced by a high dose of morphine. This study confirms our earlier postulate that morphine at 4 mg/kg, sc, induces an increase in body temperature primarily via mu opioid receptors in the brain and a high dose (30 mg/kg) of morphine administered sc produces a decrease primarily through kappa opioid receptors in the brain.