Adenosine A1, but not A2, Receptor Blockade Increases Anxiety and Arousal in Zebrafish
Adenosine A1, but not A2, Receptor Blockade Increases Anxiety and Arousal in Zebrafish
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DOI：
10.1111/j.1742-7843.2011.00710.x
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发表时间：
2011-09-01
影响因子：
3.1
通讯作者：
Herculano, Anderson M.
中科院分区：
文献类型：
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作者：
Maximino, Caio;Lima, Monica G.;Herculano, Anderson M.
腺苷能系统与类焦虑状态有关，因为咖啡因可以引起人类的焦虑状态。咖啡因是A(1)和A(2)腺苷受体的拮抗剂，但目前尚不清楚焦虑是由A(1)和A(2)腺苷受体中的一个还是两者共同介导的。由于腺苷能系统相当保守，我们选择使用斑马鱼来探索这些问题，斑马鱼是遗传学和发育生物学中广泛使用的模式生物。斑马鱼腺苷1.2A.1和2A.2受体保存TM6和TM7中的组氨酸残基，这些残基负责与牛A1受体的亲和力。本文研究了咖啡因、A(1)受体拮抗剂PACPX和A(2)受体拮抗剂1，3-二甲基-1-丙叉黄嘌呤(DMPX)对斑马鱼焦虑样行为和运动活动的影响，并评价了这些药物对色素聚集的影响。咖啡因在100 mg/kg剂量下增加焦虑，而在10 mg/kg剂量下增加运动。10 mg/kg和100 mg/kg剂量均可诱导色素聚集。PACPX在6 mg/kg剂量时增加焦虑，在0.6 mg/kg和6 mg/kg剂量下诱导色素聚集，但不产生运动作用。反过来，DMPX在6 mg/kg剂量下增加了小鼠的活动，但对色素聚集或焦虑样行为没有任何影响。这些结果表明，阻断A(1)-R而不是A(2)-R可引起焦虑和自主神经觉醒，而阻断A(2)-R则引起多动。因此，与啮齿动物一样，咖啡因的焦虑和唤醒作用可能是通过斑马鱼的A(1)受体介导的，其运动激活作用可能是通过A(2)受体介导的。
Adenosinergic systems have been implicated in anxiety-like states, as caffeine can induce a state of anxiety in human beings. Caffeine is an antagonist at A(1) and A(2) adenosine receptors but it remains unclear whether anxiety is mediated by one or both of these. As the adenosinergic system is rather conserved, we opted to pursue these questions using zebrafish, a widely used model organism in genetics and developmental biology. Zebrafish adenosine 1. 2A.1 and 2A.2 receptors conserve histidine residues in TM6 and TM7 that are responsible for affinity in bovine A1 receptor. We investigated the effects of caffeine, PACPX (an A(1) receptor antagonist) and 1,3-dimethyl-1-propargylxanthine (DMPX) (an A(2) receptor antagonist) on anxiety-like behaviour and locomotor activity of zebrafish in the scototaxis test as well as evaluated the effects of these drugs on pigment aggregation. Caffeine increased anxiety at the dose of 100 mg/kg, while locomotion at the dose of 10 mg/kg was increased. Both doses of 10 and 100 mg/kg induced pigment aggregation. PACPX, on the other hand, increased anxiety at a dose of 6 mg/kg and induced pigment aggregation at the doses of 0.6 and 6 mg/kg, but did not produce a locomotor effect. DMPX, in turn, increased locomotion at the dose of 6 mg/kg but did not produce any effect on pigment aggregation or anxiety- like behaviour. These results indicate that blockade of A(1)-R, but not A(2)-R, induces anxiety and autonomic arousal, while the blockade of A(2)-R induces hyperlocomotion. Thus, as in rodents, caffeine's anxiogenic and arousing effects are probably mediated by A(1) receptors in zebrafish and its locomotor activating effect is probably mediated by A(2) receptors.