Department of Physiology, School of Allied Health Sciences, Kitasato University, 1-15-1, Kitasato Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
Physiol Behav. 2019 May 15;204:10-19. doi: 10.1016/j.physbeh.2019.02.006. Epub 2019 Feb 6.
The dopaminergic neural system plays a crucial role in motor regulation as well as regulation of anxiety-related behaviors. Although rats with neonatal dopamine depletion exhibit motor hyperactivity and have been utilized as animal models of attention deficit hyperactivity disorder, characterization of their behavior under anxiogenic conditions is lacking. In the present study, we investigated behavioral responses to anxiogenic stimuli in young adult rats with neonatal dopamine depletion using the open field (OF), elevated plus maze (EPM), and light/dark (L/B) box tests. The OF and EPM tests were performed under low-light and bright-light conditions. The ameliorative effects of pretreatment with methamphetamine (MAP) or atomoxetine (ATX) on abnormal behaviors induced by neonatal dopamine depletion were also assessed. Rats that underwent 6-hydroxydopamine treatment 4 day after birth showed significant increases in motor activity and decreases in anxiety-related behaviors in OF tests under both conditions and in EPM tests under bright-light conditions. Furthermore, rats with neonatal dopamine depletion did not show normal behavioral responsiveness to changes in the intensity of anxiogenic stimuli. Pretreatment with MAP (4 mg/kg) and ATX (1.2 mg/kg/day) ameliorated motor hyperactivity but not abnormal anxiety-related behaviors. These results suggest that the dopaminergic system plays a crucial role in the development of neural networks involved in locomotion as well as in those involved in anxiety-related behavior. The results indicate that the mechanisms underlying the abnormal anxiolytic responses partially differ from those underlying motor hyperactivity.
多巴胺能神经系统在运动调节以及焦虑相关行为的调节中起着至关重要的作用。虽然新生期多巴胺耗竭的大鼠表现出运动过度，并且已被用作注意缺陷多动障碍的动物模型，但它们在焦虑刺激下的行为特征尚不清楚。在本研究中，我们使用旷场（OF）、高架十字迷宫（EPM）和明暗（L/B）箱测试，研究了年轻成年期新生期多巴胺耗竭大鼠对焦虑性刺激的行为反应。OF 和 EPM 测试在低光和强光条件下进行。还评估了预处理给予苯丙胺（MAP）或托莫西汀（ATX）对新生期多巴胺耗竭引起的异常行为的改善作用。出生后 4 天接受 6-羟多巴胺处理的大鼠在两种条件下的 OF 测试和强光条件下的 EPM 测试中表现出运动活动明显增加，焦虑相关行为减少。此外，新生期多巴胺耗竭的大鼠对焦虑性刺激强度变化的正常行为反应没有表现出来。MAP（4mg/kg）和 ATX（1.2mg/kg/天）预处理可改善运动过度，但不能改善异常的焦虑相关行为。这些结果表明，多巴胺能系统在参与运动的神经网络以及参与焦虑相关行为的神经网络的发育中起着至关重要的作用。结果表明，异常的抗焦虑反应的机制部分不同于运动过度的机制。
