Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments.
Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments.
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DOI：
10.1016/j.aquatox.2013.12.005
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发表时间：
2014-06
影响因子：
4.5
通讯作者：
Gould, Georgianna G.
中科院分区：
文献类型：
--
作者：
Connors, Kristin A.;Valenti, Theodore W.;Lawless, Kelly;Sackerman, James;Onaivi, Emmanuel S.;Brooks, Bryan W.;Gould, Georgianna G.
关键词：
氟西汀等选择性血清素再摄取抑制剂 (SSRI) 存在并在水生生态系统中生物蓄积的发现激发了对鱼类血清素转运蛋白 (SERT) 和 SSRI 敏感行为变化的研究，作为与风险评估相关的不良结果。许多 SSRI 还作用于血清素 5-HT1A 受体。由于利用这种作用可能会改善临床抑郁症和其他精神疾病的治疗，因此引入了激动 5-HT1A 和阻断 SERT 的新型多模式药物。在哺乳动物中，5-HT1A 和 CB 激动剂（例如丁螺环酮和 WIN55,212-2）可减少焦虑行为。免疫学和行为证据表明，5-HT1A 样受体在斑马鱼 (Danio rerio) 中可能具有类似的功能，但其药理学特性尚未得到很好的表征。在此，我们将斑马鱼大脑中与 5-HT1A 样位点结合的 [3H] 8-羟基-2-二正丙氨基四氢化萘 (8-OH-DPAT) 的密度与类似的 Gαi/o 偶联大麻素受体的密度进行了比较。 [3H] 8-OH-DPAT 在下丘脑、视顶盖和端脑中的特异性结合为 176 ± 8、275 ± 32 和 230 ± 36 fmol/mg 蛋白质。 [3H] WIN55,212-2 结合密度在这些相同的大脑区域中较高，分别为 6 ± 0.3、5.5 ± 0.4 和 7.3 ± 0.3 pm/mg 蛋白质。水生明暗十字迷宫用于检查 5-HT1A 和 CB 受体激动剂对斑马鱼新奇焦虑的行为影响。急性暴露于 5-HT1A 部分激动剂丁螺环酮 (50 mg/L) 或饮食暴露于 WIN55,212-2 (7 μg/周) 时，斑马鱼比对照组花费更多时间和/或更频繁地进入白臂 (p < 0.05)。急性暴露于 0.5-50 mg/L 的 WIN55,212-2，流动性降低。这些行为研究结果表明，阿齐酮类药物与大麻素激动剂一样，对新环境中的鱼类具有抗焦虑和/或镇静作用。这些观察结果凸显了未来需要考虑阿扎匹隆和多模式抗抑郁药潜在的生态风险。
The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitolizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [3H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of simalarly Gαi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176 ± 8, 275 ± 32, and 230 ± 36 fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [3H] WIN55,212-2 binding density was higher in those same brain regions at 6 ± 0.3, 5.5 ± 0.4 and 7.3 ± 0.3 pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50 mg/L), or dietary exposure to WIN55,212-2 (7 μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p < 0.05). Acute exposure to WIN55,212-2 at 0.5-50 mg/L, reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future.
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影响因子：
10.7
作者：
Brunet, Frederic G.;Roest Crollius, Hugues;Robinson-Rechavi, Marc
通讯作者：
Robinson-Rechavi, Marc
影响因子：
3.5
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Correa-De-Araujo, R;Miller, E;Trinh, Y
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2.9
作者：
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通讯作者：
WOOTEN, GF
影响因子：
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作者：
Airhart, Mark J.;Lee, Deborah H.;Skalko, Richard G.
通讯作者：
Skalko, Richard G.
影响因子：
3.4
作者：
Braida, Daniela;Limonta, Valeria;Sala, Mariaelvina
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Sala, Mariaelvina