Department of Neurobiology & Anatomy, University of Texas-Houston, Medical School, Houston, TX 77030, USA.
Behav Brain Res. 2012 Jan 1;226(1):8-17. doi: 10.1016/j.bbr.2011.08.027. Epub 2011 Aug 25.
Methylphenidate (MPD) is the most widely used drug in the treatment of attention-deficit hyperactivity disorder (ADHD). ADHD has a high incidence in children and can persist in adolescence and adulthood. The relation between sex and the effects of acute and chronic MPD treatment was examined using adolescent male and female rats from three genetically different strains: spontaneously hyperactive rat (SHR), Wistar-Kyoto (WKY) and Sprague-Dawley (SD). Rats from each strain and sex were randomly divided into a control group that received saline injections and three MPD groups that received either 0.6 or 2.5 or 10mg/kg MPD injections. All rats received saline on experimental day 1 (ED1). On ED2 to ED7 and ED11, the rats were injected either with saline or MPD and received no treatment on ED8-ED10. The open field assay was used to assess the dose-response of acute and chronic MPD administration. Significant sex differences were found. Female SHR and SD rats were significantly more active after MPD injections than their male counterparts, while the female WKY rats were less active than the male WKY rats. Dose dependent behavioral sensitization or tolerance to MPD treatment was not observed for SHR or SD rats, but tolerance to MPD was found in WKY rats for the 10mg/kg MPD dose. The use of dose-response protocol and evaluating different locomotor indices provides the means to identify differences between the sexes and the genetic strain in adolescent rats. In addition these differences suggest that the differences to MPD treatment between the sexes are not due to the reproductive hormones.
哌醋甲酯（MPD）是治疗注意缺陷多动障碍（ADHD）最常用的药物。ADHD 在儿童中的发病率很高，并可在青少年和成年期持续存在。本研究使用来自三种不同遗传背景的青少年雄性和雌性大鼠（自发性多动大鼠、Wistar-Kyoto 大鼠和 Sprague-Dawley 大鼠）来研究性别与急性和慢性 MPD 治疗效果的关系。来自每个品系和性别的大鼠被随机分为对照组（接受生理盐水注射）和三个 MPD 组（接受 0.6、2.5 或 10mg/kg MPD 注射）。所有大鼠在实验第 1 天（ED1）接受生理盐水注射。在 ED2-ED7 和 ED11 天，大鼠接受生理盐水或 MPD 注射，在 ED8-ED10 天不接受任何治疗。利用旷场实验评估急性和慢性 MPD 给药的剂量反应。结果发现了显著的性别差异。与雄性相比，MPD 注射后雌性 SHR 和 SD 大鼠的活动明显增加，而雌性 WKY 大鼠的活动则比雄性 WKY 大鼠少。未观察到 SHR 或 SD 大鼠对 MPD 治疗的剂量依赖性行为敏化或耐受，但 WKY 大鼠对 10mg/kg MPD 剂量出现了耐受。使用剂量反应方案和评估不同的运动指标，为鉴定青少年大鼠中性别和遗传背景之间的差异提供了手段。此外，这些差异表明，性别之间对 MPD 治疗的差异不是由于生殖激素引起的。
