Evidence that μ-opioid receptors mediate midbrain “stimulation-produced analgesia” in the freely moving rat
Evidence that μ-opioid receptors mediate midbrain “stimulation-produced analgesia” in the freely moving rat
复制标题
μ-阿片受体在自由活动的大鼠中介导中脑“刺激产生的镇痛”的证据
DOI：
10.1016/0306-4522(87)92967-8
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发表时间：
1987
期刊：
影响因子：
3.3
通讯作者：
A. Herz
中科院分区：
文献类型：
--
作者：
M. Millan;A. Czzonkowski;A. Herz
在自由活动的大鼠中脑腹侧的电刺激导致对伤害性热和伤害性压力的抗伤害性感受。反复刺激与刺激的抗伤害性功效的进行性丧失相关。适应（“耐受”）刺激的大鼠显示，低剂量全身应用的选择性μ-阿片激动剂吗啡的抗伤害感受效力显著降低。与此不同的是，选择性κ激动剂反式-3，4-二氯-N-甲基-N-[2-（1-吡咯烷基）环己基]苯乙酰胺（U 50488 H）的抗伤害感受作用没有改变。在存在纳洛酮的情况下，通过微型泵以低剂量皮下给药7天，吗啡的抗伤害性作用被消除，而U 50488 H的抗伤害性作用没有减弱：这反映了μ受体的选择性阻断。接受纳洛酮的大鼠在中脑电刺激后未能产生抗伤害感受。移除泵导致对吗啡的抗伤害性作用的超敏反应，但对U 50488 H不敏感。同样，中脑刺激产生的抗伤害感受增强。这些数据表明：（1）与κ受体激动剂相比，中脑刺激产生的镇痛对μ受体选择性交叉耐受（2）对μ受体选择性的极低剂量纳洛酮阻断中脑刺激产生的镇痛，和（3）慢性纳洛酮治疗导致与κ激动剂相比对μ激动剂的选择性超敏感性和中脑刺激产生的镇痛作用的增强。这些数据表明μ-阿片受体介导大鼠中脑刺激产生的镇痛作用对抗有害热和有害压力。
Electrical stimulation of the ventral midbrain in freely moving rats led to an antinociception against both noxious heat and noxious pressure. Recurrent stimulation was associated with a progressive loss of the antinociceptive efficacy of stimulation. Rats adapted (“tolerant”) to stimulation revealed a significant reduction in the antinociceptive potency of a low dose of the systemically applied selective μ-opioid agonist, morphine. In distinction, the antinociceptive effect of the selective κ-agonist, trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide(U50488H) was not modified. In the presence of naloxone, delivered subcutaneously via minipumps at a low dose for 7 days, the antinociceptive action of morphine was abolished, whereas that of U50488H was not attenuated: this reflects the selective blockade of μ-receptors. Rats receiving naloxone failed to develop an antinociception upon midbrain electrical stimulation. Removal of the pumps led to a supersensitivity to the antinociceptive effects of morphine but not U50488H. Similarly, midbrain stimulation-produced antinociception was enhanced.These data demonstrate that(1)midbrain stimulation-produced analgesia is selectively cross-tolerant to a μ- as compared to a κ-agonist(2)a very low dose of naloxone selective for the μ-receptor blocks midbrain stimulation-produced analgesia, and(3)chronic naloxone treatment leads to a selective supersensitivity to a μ-agonist as compared to a κ-agonist and an enhancement of midbrain stimulationproduced analgesia.Collectively, the data indicate that a μ-opioid receptor mediates midbrain stimulation-produced analgesia in the rat against both noxious heat and noxious pressure.
纳曲酮诱导的阿片受体上调的神经化学和功能相关性。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Tempel,A;Gardner,EL;Zukin,RS
通讯作者：
Zukin,RS
阿片受体调节的神经化学相关性。
影响因子：
5.8
作者：
Zukin,RS;Tempel,A
通讯作者：
Tempel,A