Prenatal morphine exposure decreases analgesia but not K+ channel activation
Prenatal morphine exposure decreases analgesia but not K+ channel activation
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DOI：
10.1097/00001756-200302100-00016
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发表时间：
2003-02-10
期刊：
影响因子：
1.7
通讯作者：
Tao, PL
中科院分区：
文献类型：
--
作者：
Chiou, LC;Yeh, GC;Tao, PL
本研究探讨了产前给予吗啡可能引起的脊髓上适应性变化，包括吗啡诱导的脊髓上抗伤害作用、脑内μ阿片受体的密度和亲和力以及吗啡对离体脑片细胞的作用。通过激活中脑导水管周围灰质（PAG）中的K+通道来评估吗啡的细胞作用，PAG是吗啡脊髓上镇痛作用的关键区域。雌性大鼠在交配前7天以2 mg/kg剂量接受吗啡给药。在妊娠期间和分娩后继续给药，剂量每2周增加1 mg/kg。在p14天的后代中进行实验。产前吗啡暴露诱导耐受脊髓上吗啡诱导甩尾反应。吗啡或生理盐水处理的母鼠之间全脑中[H-3]DAIMGC的结合亲和力和最大结合没有显著差异。放射自显影分析表明，吗啡后代纹状体，丘脑和杏仁核的μ阿片受体密度降低，但在中脑，丘脑，海马或皮质。在腹外侧PAG神经元，吗啡激活内向整流K+通道，在59%的记录吗啡后代的神经元。无论是K+通道激活的幅度，也不敏感的神经元的百分比是不同的盐水和吗啡处理的后代。它的结论是，产前吗啡暴露诱导耐受脊髓上的镇痛和这种耐受性是不归因于在中脑导水管周围灰质的μ-阿片受体密度或受体功能耦合效率的变化。
The present study has investigated the possible supraspinal adaptive changes induced by prenatal administration of morphine, including morphine-induced supraspinal antinociception in vivo, the density and binding affinity of mu-opioid receptors in the brain and the cellular action of morphine in brain slices in vitro. The cellular action of morphine was assessed by its activation of K+ channels in the ventrolateral periaqueductal gray (PAG), a crucial area for the supraspinal analgesic effect of morphine. Female rats were treated with morphine 7 days before mating at 2 mg/kg. The treatment was continued during pregnancy and after delivery at doses which increased by I mg/kg every 2 weeks. Experiments were conducted in the offspring at p14 days. Prenatal morphine exposure induced tolerance to supraspinal morphine-induced tail-flick response. The binding affinity and maximal binding of [H-3]DAIMGC) in whole brain were not significant different between the morphine- or saline-treated dams. Autoradiographic analysis shows that the mu-opioid receptor density was decreased in the striatum, thalamus and amygdala but not in the midbrain, nucleus accumbens, hippocampus or cortex in morphine offspring. In ventrolateral PAG neurons, morphine activated inwardly rectifying K+,channels in 59% of recorded neurons of morphine offspring. Neither the magnitude of K+ channel activation nor the percentage of sensitive neurons was different between the saline- and morphine-treated offspring. It is concluded that prenatal morphine exposure induces tolerance to supraspinal analgesia and this tolerance is not attributed to a change in the mu-opioid receptor density or the receptor-function coupling efficiency in the midbrain periaqueductal gray.