Dopaminergic control of anxiety in young and aged zebrafish.
Dopaminergic control of anxiety in young and aged zebrafish.
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DOI：
10.1016/j.pbb.2017.01.005
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Zhdanova IV
中科院分区：
文献类型：
--
作者：
Kacprzak V;Patel NA;Riley E;Yu L;Yeh JJ;Zhdanova IV
多巴胺转运蛋白（DAT）表达的变化，或多巴胺受体的敏感性，与衰老和药物滥用有关，可能是这两种疾病共同的一些症状的基础。在这项研究中，我们探讨了多巴胺能系统在衰老和急性可卡因暴露的焦虑效应中的作用，通过比较不同年龄的野生型（WT）和DAT敲除斑马鱼（DAT-KO）的行为表型。为了确定焦虑状态中特定多巴胺受体的参与，采用D1（SCH 23390）和D2/D3（舒必利）的拮抗剂。我们确定，DAT-KO导致慢性焦虑样状态，被视为底部居住和趋触性的增加。衰老和急性可卡因给药产生了类似的效果，两者都导致DAT mRNA丰度降低（qPCR）。抑制D1活性抵消了与DAT缺陷相关的焦虑样效应，独立于其起源。D2/D3受体的抑制减少了年轻DAT-KO的焦虑，增强了WT中可卡因的致焦虑作用，但不影响老年WT或DAT-KO鱼。这些发现提供了新的证据表明多巴胺能系统在焦虑样状态中起着关键作用，并表明成年斑马鱼为阐明焦虑的分子机制和抗焦虑药物筛选平台提供了敏感的昼夜脊椎动物模型。
Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wildtype (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO results in a chronic anxiety-like state, seen as an increase in bottom-dwelling and thigmotaxis. Similar effects were produced by aging and acute cocaine administration, both leading to reduction in DAT mRNA abundance (qPCR). Inhibition of D1 activity counteracted the anxiety-like effects associated with DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced anxiety in young DAT-KO, enhanced the anxiogenic effects of cocaine in WT, but did not affect aged WT or DAT-KO fish. These findings provide new evidence that the dopaminergic system plays a critical role in anxiety-like states, and suggest that adult zebrafish provide a sensitive diurnal vertebrate model for elucidating the molecular mechanisms of anxiety and a platform for anxiolytic drug screens.
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影响因子：
2.7
作者：
Egan, Rupert J.;Bergner, Carisa L.;Hart, Peter C.;Cachat, Jonathan M.;Canavello, Peter R.;Elegante, Marco F.;Elkhayat, Salem I.;Bartels, Brett K.;Tien, Anna K.;Tien, David H.;Mohnot, Sopan;Beeson, Esther;Glasgow, Eric;Amri, Hakima;Zukowska, Zofia;Kalueff, Allan V.
通讯作者：
Kalueff, Allan V.
斑马鱼（Danio Rerio）的焦虑度量：黑色/白色偏好和新型坦克测试的解离。
影响因子：
3.7
作者：
Blaser RE;Rosemberg DB
通讯作者：
Rosemberg DB
影响因子：
2.6
作者：
Lee, Lan-Ting;Tsai, Hsin Chun;Yang, Yen Kuang
通讯作者：
Yang, Yen Kuang
影响因子：
3.7
作者：
Joyce PR;Stephenson J;Kennedy M;Mulder RT;McHugh PC
通讯作者：
McHugh PC
DOI：
10.1073/pnas.191380698
发表时间：
2001-09-25
影响因子：
11.1
作者：
Darland, T;Dowling, JE
通讯作者：
Dowling, JE