Dissociation between sex differences in the immunological, behavioral, and physiological effects of kappa- and delta-opioids in Fischer rats.
Dissociation between sex differences in the immunological, behavioral, and physiological effects of kappa- and delta-opioids in Fischer rats.
复制标题
费舍尔大鼠中κ-阿片类药物和δ-阿片类药物对免疫学、行为和生理学影响的性别差异之间的分离。
DOI：
10.1007/s00213-005-0267-1
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发表时间：
2006
影响因子：
3.4
通讯作者：
Lysle,DonaldT
中科院分区：
文献类型：
--
作者：
Elliott,JayC;Picker,MitchellJ;Sparrow,AndrewJ;Lysle,DonaldT
个体的性别会对阿片类药物的敏感性产生深远的影响。最近，我们的实验室提供了第一个证据，表明女性可能比男性对μ阿片类药物的免疫改变作用更敏感。然而，目前尚不清楚κ阿片和δ阿片是否在免疫反应中产生性二态效应。目的本研究试图利用记忆-T细胞依赖的体内炎症反应接触超敏反应来确定κ阿片和δ阿片是否在男性和女性中产生不同的免疫效应。由于阿片类药物效应大小的性别差异可能因结果而异，因此还进行了额外的实验，以比较κ-和δ-阿片类药物与其他行为和生理效应的免疫效应。材料和方法在雄性和雌性Fischer大鼠中诱导接触性超敏反应。在诱发CHS之前，动物被给予选定剂量的κ-阿片螺旋体(0.2-20 mg/kg)、δ-阿片SNC80(1-10 mg/kg)或赋形剂。此外，还评价了螺妥林对男性和女性的抗伤害作用和利尿作用，以及SNC80的运动作用。结果螺妥林对女性CHS的促进作用明显大于男性，但男女的抗伤害和利尿作用相当。相反，SNC80对男女的CHS进程没有显著影响，但女性对其运动刺激作用明显敏感。结论这些结果表明，女性比男性对螺旋多林改变CHS的作用更敏感，性别差异在阿片类药物诱导的性别差异的大小和方向上具有结果依赖性。
RationaleThe sex of the individual can have a profound effect on sensitivity to the effects of opioids. Recently, our laboratory provided the first evidence that females may be more sensitive to the immune-altering effects of μ-opioids than males. However, it remains unknown whether κ- and δ-opioids produce sexually dimorphic effects on immune responses.ObjectiveThe present study sought to determine whether κ- and δ-opioids produce differential immunological effects in males and females using the memory-T-cell-dependent in vivo inflammatory response contact hypersensitivity (CHS). As sex differences in the magnitude of opioid effects can be outcome-specific, additional experiments were conducted to compare the immunological effects of κ- and δ-opioids with other behavioral and physiological effects.Materials and methodsContact hypersensitivity was induced in male and female Fischer rats. Prior to elicitation of CHS, animals were administered selected doses of the κ-opioid spiradoline (0.2–20 mg/kg), δ-opioid SNC80 (1–10 mg/kg), or vehicle. The antinociceptive and diuretic effects of spiradoline were also assessed in males and females, as were the locomotor effects of SNC80.ResultsSpiradoline produced significantly greater enhancement of CHS in females than males, but produced comparable antinociceptive and diuretic effects in both sexes. By contrast, SNC80 did not significantly affect the course of CHS in either sex, but females were significantly more sensitive to its locomotor stimulatory effects.ConclusionsThese results demonstrate that females are more sensitive than males to the CHS-altering effects of spiradoline and that sex differences in the magnitude and direction of opioid-induced sex differences are outcome dependent.