Sex differences in striatal dopaminergic function within heterozygous mutant dopamine transporter knock-out mice
Sex differences in striatal dopaminergic function within heterozygous mutant dopamine transporter knock-out mice
复制标题
DOI：
10.1007/s00702-007-0017-0
复制
发表时间：
2008-06-01
影响因子：
3.3
通讯作者：
Dluzen, Dean E.
中科院分区：
文献类型：
--
作者：
Ji, Jing;Dluzen, Dean E.
研究了多巴胺转运蛋白（DAT）等位基因（+/- DAT）缺失是否会差异性地改变雄性和雌性小鼠之间钾和甲基苯丙胺（MA）刺激时纹状体多巴胺（DA）和二羟苯乙酸（DOPAC）浓度以及DA释放的问题。与野生型（+/+）对照组和雄性+/- DAT小鼠相比，雌性+/- DAT小鼠的纹状体DA和DOPAC浓度显著降低。没有这样的变化，从嗅结节表明，这些影响可能是特定的纹状体。在雄性和雌性+/- DAT小鼠中钾刺激的DA增加，并且从+/- DAT雌性获得最大刺激的DA，尽管这些小鼠显示出最低的DA浓度。雄性和雌性+/-小鼠中MA诱发的DA增加。虽然MA诱发的DA在+/+雄性与+/+雌性中显著增加，但+/-雌性显示出最高的DA反应，从而显示出在野生型条件下观察到的结果逆转。这些调查结果表明：（1）DAT的缺乏与受试者的性别相互作用，（2）+/- DAT女性在多巴胺能反应中显示出更极端的变化，以及（3）当检查敲除条件之间的差异时，考虑诸如性别等变量的重要性。
The issue of whether a deletion of the dopamine transporter (DAT) allele (+/- DAT) would differentially alter striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations and DA release upon potassium and methamphetamine (MA) stimulation between male and female mice was examined. Striatal DA and DOPAC concentrations of female +/- DAT mice were significantly decreased as compared with wild type (+/+) controls and male +/- DAT mice. No such changes were obtained from the olfactory tubercle suggesting that these effects might be specific for the striatum. Potassium-stimulated DA was increased in male and female +/- DAT mice and maximally stimulated DA was obtained from +/- DAT females, although these mice showed the lowest DA concentrations. MA-evoked DA was increased in male and female +/- mice. While MA-evoked DA was significantly increased in +/+ males versus +/+ females, the +/- females showed the highest DA responses, thereby showing a reversal in the results seen in wild-type conditions. These findings indicate: (1) that a deficiency in the DAT interacts with the sex of the subject, (2)+/- DAT females show more extreme changes in dopaminergic responses, and (3) the importance for considering such variables such as sex when examining differences among knock-out conditions.