Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC)
Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC)
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DOI：
10.1016/j.ntt.2007.07.005
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发表时间：
2007-11-01
影响因子：
2.9
通讯作者：
Skalko, Richard G.
中科院分区：
文献类型：
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作者：
Airhart, Mark J.;Lee, Deborah H.;Skalko, Richard G.
本研究考察了选择性5-羟色胺再吸收抑制剂（SSRI）、百忧解（PROZAC）对发育中的斑马鱼自发游泳活动（SSA）个体发育的影响。斑马鱼运动行为的发展包括四种连续的运动模式，它们在受精后1-5天（dpf）内发展，最终模式SSA在4-5 dpf建立。在阶段特异性实验中，从受精后24小时（hpf）开始，将幼虫暴露于4.6 μ M氟西汀24小时，并延伸至5 dpf。对SSA或运动发育的早期阶段没有影响，即，自发卷曲、诱发卷曲和爆发性游泳。氟西汀暴露于3 dpf 24 h导致SSA一过性降低，直至7 dpf，8 dpf完全恢复。在4或5 dpf暴露于4.6 μ M氟西汀24 h的Larvae在第6天显示SSA显著降低，直到14 dpf没有恢复。虽然SSA在氟西汀暴露后24 h受到显著影响，但对胸鳍运动几乎没有影响。这些结果表明，4.6 μ M的氟西汀暴露对4 dpf和5 dpf幼虫具有阶段特异性和长期影响。进行逆转录聚合酶链反应（RT-PCR），以确定在1-6 dpf的发育胚胎/幼虫中5-羟色胺转运蛋白（SERT）转录本和5-羟色胺1A（5-HT 1A）受体转录本的相对水平。这两种转录本都存在于24 hpf，SERT转录本的相对浓度在发育时间范围内没有变化。然而，5-HT 1A受体转录物的相对浓度显示出两层浓度模式。RT-PCR也被用来检测潜在的变化，SERT和5-HT 1A受体转录本在6 dpf幼虫后，24小时暴露于4.6 μ M氟西汀5 dpf。分别分析了CNS的三个独立区域，两个定义的脑区域和脊髓。暴露于氟西汀后，这两个大脑区域对转录水平没有影响，然而，脊髓的两个转录水平均显着下降。这些结果表明，氟西汀暴露后脊髓中SERT和5-HT 1A受体转录物浓度降低与SSA降低之间存在相关性。(c)2007年爱思唯尔公司All rights reserved.
This study examines the effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (PROZAC), on the ontogeny of spontaneous swimming activity (SSA) in developing zebrafish. The development of zebrafish motor behavior consists of four sequential locomotor patterns that develop over 1-5 days post fertilization (dpf), with the final pattern, SSA, established at 4-5 dpf In stage specific experiments, larvae were exposed to 4.6 mu M fluoxetine for 24 h periods beginning at 24 h post fertilization (hpf) and extending through 5 dpf From 1-3 dpf, there was no effect on SSA or earlier stages of motor development, i.e., spontaneous coiling, evoked coiling and burst swimming. Fluoxetine exposure at 3 dpf for 24 h resulted in a transient decrease in SSA through 7 dpf with a complete recovery by 8 dpf. Larvae exposed to 4.6 mu M fluoxetine for 24 h on 4 or 5 dpf showed a significant decrease in SSA by day 6 with no recovery through 14 dpf Although SSA was significantly affected 24 h after fluoxetine exposure, there was little or no effect on pectoral fin movement. These results demonstrate both a stage specific and a long term effect of 4.6 mu M fluoxetine exposure in 4 and 5 dpf larvae. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the relative levels of a serotonin transporter protein (SERT) transcript and the serotonin 1A (5-HT1A) receptor transcript in developing embryos/larvae over 1-6 dpf. Both transcripts were present at 24 hpf with the relative concentration of SERT transcript showing no change over the developmental time range. The relative concentration of the 5-HT1A receptor transcript, however, showed a two-tiered pattern of concentration. RT-PCR was also used to detect potential changes in the SERT and 5-HT1A receptor transcripts in 6 dpf larvae after a 24 h exposure to 4.6 mu M fluoxetine on 5 dpf. Three separate regions of the CNS were individually analyzed, two defined brain regions and spinal cord. The two brain regions showed no effect on transcript levels subsequent to fluoxetine exposure, however, the spinal cord showed a significant decrease in both transcripts. These results suggest a correlation between decreased concentration of SERT and 5-HT1A receptor transcripts in spinal cord and decreased SSA subsequent to fluoxetine exposure. (c) 2007 Elsevier Inc. All rights reserved.