Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, 6431 Fannin St., Houston, TX, 77030, USA,
J Neural Transm (Vienna). 2014;121(3):327-45. doi: 10.1007/s00702-013-1101-2. Epub 2013 Nov 20.
Methylphenidate (MPD) is used to treat ADHD and as a cognitive enhancement and recreationally. MPD's effects are not fully understood. One of the sites of psychostimulant action is the ventral tegmental area (VTA). The VTA neuronal activity was recorded from freely behaving rats using a wireless system. 51 animals were divided into groups: saline, 0.6, 2.5, and 10.0 mg/kg MPD. The same repetitive MPD dose can elicit either behavioral sensitization or tolerance; thus the evaluation of the VTA neuronal activity was based on the animals' behavioral response to chronic MPD exposure: animals exhibiting behavioral tolerance or sensitization. Acute MPD elicits dose-related increases in behavioral activity. About half of the animals exhibited behavioral sensitization or tolerance to each of the MPD doses. 361 units were recorded from the VTA and exhibited similar spike shape on experimental day 1 (ED1) and on ED10. 71, 84, and 79 % of VTA units responded to acute 0.6, 2.5, and 10.0 mg/kg MPD, respectively. The neuronal baseline activity at ED10 was significantly modified in 94, 95, and 100 % of VTA units following 0.6, 2.5 and 10.0 mg/kg MPD, respectively. Following chronic MPD exposure, 91, 98, and 100 % exhibit either electrophysiological tolerance or sensitization of 0.6, 2.6, or 10.0 mg/kg MPD, respectively. In conclusion, the chronic administration of the same dose of MPD caused some animals to exhibit behavioral sensitization and other animals to exhibit tolerance. The VTA units recorded from animals exhibiting behavioral sensitization responded significantly differently to MPD from animals that exhibited behavioral tolerance.
哌醋甲酯（MPD）用于治疗 ADHD 以及作为认知增强剂和娱乐性药物。MPD 的作用尚未完全了解。其中一个精神兴奋剂作用的部位是腹侧被盖区（VTA）。使用无线系统从自由活动的大鼠中记录 VTA 神经元活动。将 51 只动物分为以下几组：生理盐水、0.6、2.5 和 10.0mg/kg MPD。相同的重复 MPD 剂量可能会引起行为敏化或耐受；因此，VTA 神经元活动的评估基于动物对慢性 MPD 暴露的行为反应：表现出行为耐受或敏化的动物。急性 MPD 会引起行为活动的剂量相关增加。大约一半的动物对每种 MPD 剂量表现出行为敏化或耐受。从 VTA 记录了 361 个单位，在实验第 1 天（ED1）和第 10 天（ED10）表现出相似的尖峰形状。71%、84%和 79%的 VTA 单位分别对急性 0.6、2.5 和 10.0mg/kg MPD 有反应。在 ED10 时，94%、95%和 100%的 VTA 单位的神经元基线活动在分别给予 0.6、2.5 和 10.0mg/kg MPD 后显著改变。在慢性 MPD 暴露后，91%、98%和 100%分别对 0.6、2.6 或 10.0mg/kg MPD 表现出电生理耐受或敏化。总之，相同剂量的 MPD 慢性给药导致一些动物表现出行为敏化，而另一些动物表现出耐受。从表现出行为敏化的动物记录的 VTA 单位对 MPD 的反应与表现出行为耐受的动物有显著不同。
