PUBLICATION
Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC)
- Authors
- Airhart, M.J., Lee, D.H., Wilson, T.D., Miller, B.E., Miller, M.N., and Skalko, R.G.
- ID
- ZDB-PUB-070907-20
- Date
- 2007
- Source
- Neurotoxicology and teratology 29(6): 652-664 (Journal)
- Registered Authors
- Keywords
- Fluoxetine, Zebrafish, Serotonin, SERT, 5-HT1A, Spontaneous swimming
- MeSH Terms
-
- Analysis of Variance
- Animals
- Behavior, Animal/drug effects
- Central Nervous System/drug effects
- Central Nervous System/metabolism*
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects*
- Female
- Fertilization/drug effects
- Fluoxetine/toxicity*
- Gene Expression Regulation, Developmental/drug effects
- Heart Rate/drug effects
- Larva/drug effects
- Larva/metabolism*
- Locomotion/drug effects
- Motor Activity/drug effects
- Movement Disorders*/etiology
- Movement Disorders*/metabolism
- Movement Disorders*/pathology
- Receptor, Serotonin, 5-HT1A/metabolism
- Selective Serotonin Reuptake Inhibitors/toxicity*
- Serotonin/metabolism
- Serotonin Plasma Membrane Transport Proteins/metabolism
- Time Factors
- Zebrafish
- PubMed
- 17761399 Full text @ Neurotoxicol. Teratol.
- CTD
- 17761399
Citation
Airhart, M.J., Lee, D.H., Wilson, T.D., Miller, B.E., Miller, M.N., and Skalko, R.G. (2007) Movement disorders and neurochemical changes in zebrafish larvae after bath exposure to fluoxetine (PROZAC). Neurotoxicology and teratology. 29(6):652-664.
Abstract
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 muM 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 muM 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 muM 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 muM 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-HT(1A) receptor transcripts in spinal cord and decreased SSA subsequent to fluoxetine exposure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping