Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 139-742, South Korea.
Arch Pharm Res. 2013 Jan;36(1):134-40. doi: 10.1007/s12272-013-0009-6.
In previous studies we have demonstrated that the γ-aminobutryic acid-A (GABA-A) receptor antagonist oroxylin A has an awakening effect and it also represses ADHD-like behaviors (hyperactivity, impulsivity and inattention) in the spontaneously hypertensive rat (SHR) model of attention-deficit hyperactivity disorder (ADHD). We hypothesized that the effects of oroxylin A were exerted via the GABA-A receptor given the important role of the GABAergic system in ADHD. However, it is possible that aside from the GABAergic system, oroxylin A may influence other systems especially those implicated in ADHD (e.g. DAergic, etc.). To test this hypothesis, we evaluated the effects of GABA agonist, or dopamine (DA) antagonist in oroxylin A-induced alleviation of ADHD-like behaviors in SHR. SHR showed inattention and impulsivity as measured by the Y-maze and the electro-foot shock aversive water drinking tests, respectively. Oroxylin A significantly improved these behaviors, furthermore, its effect on SHR impulsivity was attenuated by haloperidol, a DA antagonist, but not by baicalein, an agonist of the GABA-A receptor. In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate, a dopamine transporter blocker, but did not influence norepinephrine uptake unlike atomoxetine, a selective NE reuptake inhibitor. Collectively, the present findings suggest that oroxylin A improves ADHD-like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported. Importantly, the present study indicates the potential therapeutic value of oroxylin A in the treatment of ADHD.
在之前的研究中，我们已经证明 γ-氨基丁酸-A（GABA-A）受体拮抗剂梓醇具有觉醒作用，并且它还能抑制自发性高血压大鼠（SHR）注意力缺陷多动障碍（ADHD）模型中的 ADHD 样行为（多动、冲动和注意力不集中）。我们假设梓醇的作用是通过 GABA-A 受体发挥的，因为 GABA 能系统在 ADHD 中起着重要作用。然而，除了 GABA 能系统之外，梓醇可能还会影响其他系统，特别是那些与 ADHD 有关的系统（例如 DA 能系统等）。为了验证这一假设，我们评估了 GABA 激动剂或多巴胺（DA）拮抗剂对梓醇减轻 SHR 中 ADHD 样行为的影响。SHR 在 Y 迷宫和电足底电击厌恶水饮试验中分别表现出注意力不集中和冲动。梓醇显著改善了这些行为，此外，其对 SHR 冲动的作用被 DA 拮抗剂氟哌啶醇减弱，但不受 GABA-A 受体激动剂白杨素的影响。体外研究表明，梓醇抑制 DA 摄取的作用类似于多巴胺转运体阻滞剂哌甲酯，但不像选择性 NE 再摄取抑制剂托莫西汀那样影响去甲肾上腺素摄取。综上所述，目前的研究结果表明，梓醇通过增强 DA 神经传递而不是如先前报道的那样调节 GABA 途径来改善 SHR 的 ADHD 样行为。重要的是，本研究表明梓醇在治疗 ADHD 方面具有潜在的治疗价值。
