Sex differences in supraspinal morphine analgesia are dependent on genotype.
Sex differences in supraspinal morphine analgesia are dependent on genotype.
复制标题
DOI：
--
复制
发表时间：
1999-06
期刊：
影响因子：
--
通讯作者：
B. Kest;Sonya G. Wilson;J. Mogil
中科院分区：
文献类型：
--
作者：
B. Kest;Sonya G. Wilson;J. Mogil
据报道，有几个变量影响吗啡镇痛效力的性别差异的表达。虽然遗传背景对吗啡镇痛的影响已被充分证明，但基因型与吗啡镇痛的性别差异的相关性很少被考虑。本研究研究了11个近交系小鼠雄性和雌性小鼠在给药后的吗啡断尾试验中的剂量-反应关系。菌株间吗啡镇痛效力差异较大，反映了基因型对该性状的重要影响。我们鉴定了三种菌株（AKR/J， C57BL/6J和SWR/J），其中雄性对吗啡镇痛作用的敏感性比雌性高3.5至7.0倍。相比之下，在CBA/J菌株中，发现雌性对吗啡的敏感性约为雄性的5倍。在所有其他菌株中，两性之间的吗啡效价估计没有统计学差异。这些数据支持了基因型、性别及其相互作用在吗啡镇痛介导中的重要性，并表明文献中关于阿片类药物性别差异的模棱两可的发现可能部分是由于使用了不同的受试者群体。AKR/J和CBA/J菌株的雌性小鼠表现出35倍的吗啡镇痛效力，而这些菌株的雄性小鼠同样敏感，这一事实有助于定位和鉴定与吗啡镇痛相关的性别特异性基因。
Several variables have been reported to affect the expression of sex differences in the analgesic potency of morphine. Although the effect of genetic background on morphine analgesia has been well documented, the relevance of genotype to sex differences in morphine analgesia has rarely been considered. The present study investigated morphine dose-response relationships in male and female mice of 11 inbred mouse strains on the tail-withdrawal test after i.c.v. administration. Large differences in morphine analgesic potency were observed between strains, reflecting the important influence of genotype on this trait. We identified three strains (AKR/J, C57BL/6J, and SWR/J) in which males displayed approximately 3.5- to 7.0-fold greater sensitivities to the analgesic effects of morphine than did their female counterparts. In contrast, in the CBA/J strain, females were found to be approximately 5-fold more sensitive to morphine than were the males. In all other strains, morphine potency estimates between the sexes were not statistically different. These data support the importance of genotype, sex, and their interaction in the mediation of morphine analgesia and suggest that equivocal findings regarding opioid sex differences in the literature may be partially accounted for by the use of different subject populations. The fact that female mice of the AKR/J and CBA/J strains exhibit 35-fold different morphine analgesic potency and that males of these strains are equally sensitive should facilitate the mapping and identification of sex-specific genes of relevance to morphine analgesia.