Fluoxetine in the marine environment: Effects on sheepshead minnow (Cyprinodon variegatus) serotonin activity and locomotor behavior
Winder, Virginia Louise
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Fluoxetine (FLX), the active ingredient in the prescription antidepressant drug Prozac (TM), is a selective serotonin reuptake inhibitor (SSRI) and is among the top 100 drugs prescribed yearly in both the United States and the United Kingdom. Fluoxetine has been found in sewage treatment plant effluent and surface waters where it has the potential to cause changes in behavior, reproduction and species interactions that can result in significant damage to aquatic ecosystems. Methods were developed to detect and quantify FLX, norfluoxetine, serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), tryptophan and melatonin in fish tissues and water using LC/MS/MS. Juvenile sheepshead minnows (Cyprinodon variegatus) were exposed to FLX with paired control groups. Fish were sacrificed at the end of the trials, and tissues were analyzed for changes in 5-HT and other neurotransmitters. Significant changes in neurotransmitter levels and activity due to treatment were observed in juvenile sheepshead minnows using repeated measures ANOVA and regression analyses. Behavioral trials were used to quantify fish locomotor activity following FLX exposure. Fluoxetine was shown to produce a significant reduction in locomotor activity at 0.3 mg L-1 at time points 1, 25, 32, 49 and 56 h post-dose. A 32-h EC50 for FLX effect on locomotor activity was calculated at 0.1549 mg L-1; an EC25 calculated for the same time point was 0.0023 mg L-1. The sublethal effect of decreased locomotor activity as related to FLX exposure could potentially result in decreased survival in fish populations in natural ecosystems. This work characterizes the acute toxicological effects of fluoxetine on the sheepshead minnow from lethal, sublethal, physiological and behavioral perspectives.