Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: Comparison with nicotine and pilocarpine effects and relationship to dopamine deficits

Abstract

Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study we tested the hypothesis that persisting effects of developmental chlorpyrifos could be detected with a brief automated assessment of startle response and that this behavioral index could be used to help determine the neurobehavioral mechanisms for persisting CPF effects. The swimming activity of adult zebrafish was assessed by a computerized video-tracking device after a sudden tap to the test arena. Ten consecutive trials (1/min) were run to determine startle response and its habituation. Additionally, habituation recovery trials were run at 8, 32 and 128 min after the end of the initial trial set. CPF-exposed fish showed a significantly (p<0.025) greater overall startle response during the 10-trial session compared to controls (group sizes: Control N=40, CPF N=24). During the initial recovery period (8 min) CPF-exposed fish showed a significantly (p<0.01) greater startle response compared to controls. To elucidate the contributions of nicotinic and muscarinic acetylcholine receptors to developmental CPF-mediated effects, the effects of developmental nicotine and pilocarpine exposure throughout the first five days after fertilization were determined. Developmental nicotine and pilocarpine exposure significantly increased startle response, though nicotine (group sizes: Control N=32, 15 mM N=12, 25 mM N=20) was much more potent than pilocarpine (group sizes: Control N=20, 100 μM N=16, 1000 μM N=12). Neither was as potent as CPF for developmental exposure increasing startle response in adulthood. Lastly, developmental CPF exposure decreased dopamine and serotonin levels and increased transmitter turnover in

Prenatal Transfer of Polybrominated Diphenyl Ethers (PBDEs) Results in Developmental Neurotoxicity in Zebrafish Larvae

“…18,33 We found no significant effects on this enzyme activity in adult fish brains. Few studies have addressed the effects of PBDEs on AChE activity in fish brains and the mechanisms of toxicity are not known.…”

Scopolamine-induced learning impairment reversed by physostigmine in zebrafish

“…Another possibility is that the effects of chlorpyrifos result from non-cholinergic mechanisms such as the interfering cellular signaling cascade (Slotkin and Seidler, 2009). However, interestingly, chlorpyrifos and pilocarpine, a muscarinic receptor agonist, both increased the startle response in 20-weekold adults when treated during the first 5 days after fertilization (Eddins et al, 2010), the former being substantially more potent than the latter; this suggests that at least a portion of chlorpyrifos' effects are mediated through the cholinergic system. Furthermore, it should be noted that chlorpyrifos has also been reported to function as a proconvulsant in the amygdala kindling in immature rats (Wurpel et al, 1993).…”

Automated High-throughput Behavioral Analyses in Zebrafish Larvae

“…Zebrafish larvae are ideally suited for high-throughput analyses because of their small size 7,8 . Software is commercially available for automated analyses of behavior in larval and adult zebrafish [9][10][11][12][13][14] . However, this software can be expensive and has limited options for measuring complex behaviors of zebrafish larvae in multi-well plates.…”