Chen J, Rinaldo L, Lim S-J, Young H, Messing R O, Choi D-S
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Genes Brain Behav. 2007 Nov;6(8):776-83. doi: 10.1111/j.1601-183X.2007.00311.x. Epub 2007 Mar 21.
Activation of adenosine receptors in the brain reduces anxiety-like behavior in animals and humans. Because nucleoside transporters regulate adenosine levels, we used mice lacking the type 1 equilibrative nucleoside transporter (ENT1) to investigate whether ENT1 contributes to anxiety-like behavior. The ENT1 null mice spent more time in the center of an open field compared with wild-type littermates. In the elevated plus maze, ENT1 null mice entered more frequently into and spent more time exploring the open arms. The ENT1 null mice also spent more time exploring the light side of a light-dark box compared with wild-type mice. Microinjection of an ENT1-specific antagonist, nitrobenzylthioinosine (nitrobenzylmercaptopurine riboside), into the amygdala of C57BL/6J mice reduced anxiety-like behavior in the open field and elevated plus maze. These findings show that amygdala ENT1 modulates anxiety-like behavior. The ENT1 may be a drug target for the treatment of anxiety disorders.
激活大脑中的腺苷受体会减少动物和人类的焦虑样行为。由于核苷转运体调节腺苷水平，我们使用缺乏1型平衡核苷转运体（ENT1）的小鼠来研究ENT1是否与焦虑样行为有关。与野生型同窝小鼠相比，ENT1基因敲除小鼠在旷场中央停留的时间更长。在高架十字迷宫中，ENT1基因敲除小鼠更频繁地进入开放臂并在其中停留更长时间进行探索。与野生型小鼠相比，ENT1基因敲除小鼠在明暗箱的亮侧探索的时间也更长。向C57BL/6J小鼠杏仁核微量注射ENT1特异性拮抗剂硝基苄硫肌苷（硝基苄巯基嘌呤核苷）可减少其在旷场和高架十字迷宫中的焦虑样行为。这些发现表明杏仁核ENT1调节焦虑样行为。ENT1可能是治疗焦虑症的药物靶点。
