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首页> 外文期刊>Neurotoxicology and teratology >Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC).
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Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC).

机译：浴暴露于氟西汀（PROZAC）后斑马鱼幼虫的运动障碍和神经化学变化。

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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 microM 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 microM 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 microM 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-HT(1A)) 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-HT(1A) receptor transcript, however, showed a two-tiered pattern of concentration. RT-PCR was also used to detect potential changes in the SERT and 5-HT(1A) receptor transcripts in 6 dpf larvae after a 24 h exposure to 4.6 microM 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 noeffect 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-HT(1A) receptor transcripts in spinal cord and decreased SSA subsequent to fluoxetine exposure.
机译：这项研究检查了选择性5-羟色胺再摄取抑制剂（SSRI），氟西汀（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由四个连续的运动模式组成，这些模式在受精后（dpf）超过1-5天发展，最终模式SSA则定为4-5 dpf。在特定阶段的实验中，幼虫从受精后（hpf）的24小时开始，暴露于4.6 microM氟西汀24小时，并持续5 dpf。从1-3 dpf开始，对SSA或运动发育的早期阶段（即自发盘绕，诱发的盘绕和爆发游泳）没有影响。氟西汀在3 dpf下暴露24 h导致SSA短暂降低至7 dpf，并完全恢复8 dpf。幼虫在4或5 dpf下暴露于4.6 microM氟西汀24小时后，到第6天，SSA显着降低，直到14 dpf仍未恢复。尽管SSA在氟西汀暴露后24小时受到显着影响，但对胸鳍运动几乎没有影响。这些结果证明了在4和5 dpf幼虫中4.6 microM氟西汀暴露的阶段特异性和长期作用。进行逆转录酶聚合酶链反应（RT-PCR）以测定1-6 dpf以上发育中的胚胎/幼虫中5-羟色胺转运蛋白（SERT）转录物和5-羟色胺1A（5-HT（1A））受体转录物的相对水平。两种转录本均以24 hpf存在，SERT转录本的相对浓度在发育时间范围内未显示变化。但是，5-HT（1A）受体转录物的相对浓度显示了两层浓度模式。在5 dpf暴露于4.6 microM氟西汀24小时后，RT-PCR还用于检测6 dpf幼虫中SERT和5-HT（1A）受体转录物的潜在变化。分别分析了CNS的三个独立区域，两个定义的大脑区域和脊髓。氟西汀暴露后，两个大脑区域对转录水平没有影响，但是，脊髓显示两个转录水平均显着降低。这些结果表明，脊髓中SERT和5-HT（1A）受体转录物的浓度降低与氟西汀接触后SSA降低之间存在相关性。

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