Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats
Midazolam attenuates the antinociception induced by D-serine or morphine at the supraspinal level in rats
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DOI：
10.1016/j.ejphar.2008.02.068
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发表时间：
2008-05-31
影响因子：
5
通讯作者：
Hashimoto, Atsushi
中科院分区：
文献类型：
--
作者：
Ito, Kenji;Yoshikawa, Masanobu;Hashimoto, Atsushi
我们最近的研究表明，脑室内给予d -丝氨酸（n -甲基- d -天冬氨酸受体甘氨酸位点的内源性选择性激动剂），单独或与吗啡联合使用，可增强尾甩反应的抗痛觉作用。虽然关于苯二氮卓类药物对阿片类药物诱导的抗痛觉的影响有各种各样的信息，但对苯二氮卓类药物对n -甲基- d-天冬氨酸受体激动剂诱导的抗痛觉的影响知之甚少。为了阐明苯二氮卓/GABA(A)、n -甲基- d -天冬氨酸和阿片受体在椎管上水平的镇痛相互作用，我们研究了苯二氮卓受体激动剂咪达唑仑（midazolam）在脑室内对d -丝氨酸或吗啡引起的抗痛觉的影响。在脑室内单独给药咪达唑仑会对苯二氮卓受体拮抗剂的甩尾反应产生痛觉过敏，氟马西尼可逆。脑室内给药咪唑安定可减弱d -丝氨酸或吗啡所致的抗痫作用。此外，咪达唑仑对d -丝氨酸或吗啡的抑制作用被氟马西尼脑室内给药所拮抗。结合d -丝氨酸和咪达唑仑分别作为n -甲基- d -天冬氨酸受体和苯二氮卓/GABAA受体甘氨酸位点的选择性激动剂的事实，这些观察结果表明NMDA和苯二氮卓/GABAA受体在脊椎上水平的抗痛觉调节中存在功能相互作用。(C) 2008 Elsevier B.V.版权所有
Our recent study has shown that the intracerebroventricular administration of D-serine, an endogenous and selective agonist for the glycine site of the N-methyl-D-aspartate receptor, alone or in combination with morphine, leads to the potentiation of antinociception on the tail-flick response. Although there is a variety of information concerning the effects of benzodiazepines on opioid-induced antinociception, little is known about the effect of benzodiazepines on the N-methyl-D-aspartate receptor agonist-induced antinociception. To clarify the analgesic interactions among the benzodiazepine/GABA(A), N-methyl-D-aspartate and opioid receptors at the supraspinal level, we investigated the effects of intracerebroventricular administration of midazolam, a benzodiazepine receptor agonist, on the antinociception evoked by the intracerebroventricular application of D-serine or morphine. The intracerebroventricular administration of midazolam alone produced hyperalgesia on the tail-flick response in a benzodiazepine receptor antagonist, flumazenil-reversible manner. The antinociception induced by the intracerebroventricular application of D-serine or morphine was attenuated by the intracerebroventricular administration of miclazolam. In addition, this inhibitory effect of midazolam on the antinociception of D-serine or morphine was antagonized by the intracerebroventricular administration of flumazenil. Together with the facts that D-serine and midazolam act as selective agonists for the glycine site of the N-methyl-D-aspartate receptor and benzodiazepine/GABAA receptor, respectively, these observations suggest a functional interaction between the NMDA and benzodiazepine/GABAA receptors in the regulation of antinociception at the supraspinal level. (C) 2008 Elsevier B.V. All rights reserved.