Deciphering the mode of action of pollutants impairing the fish larvae escape response with the vibrational startle response assay

Abstract

The escape response evoked by vibrational stimuli and its habituation, essential behaviors for fish larvae survival, can be altered by neurotoxic environmental pollutants commonly found in our aquatic ecosystems.In this study we have analyzed the suitability of the Vibrational Startle Response Assay (VSRA) to obtain mechanistic information about the mode of action (MoA) of the chemicals impairing the escape response and its habituation. As a proof of concept, the pathophysiological mechanisms behind the action of two common neurotoxic pesticides, chlorpyrifos-oxon (CPO) and imidacloprid, over their effects on arousal and habituation of the escape response were studied by using pharmacological antagonists of the nicotinic and muscarinic acetylcholine receptors, mecamylamine (MCA) and scopolamine, respectively. Furthermore, potential changes in the neurotransmitter profile were analyzed. Results revealed that whereas the effect of CPO on arousal was mainly mediated by the activation of nAChRs, its effect on habituation was mainly mediated by mAChRs. On the other hand, imidacloprid only affected larvae arousal which was found to be mediated by a cholinergic independent mechanism. No association between behavioral effects on arousal or habituation in affected larvae was found with their corresponding neurotransmitter profile. These results confirm the suitability of VSRA to provide mechanistic information about the potential MoA of neuroactive compounds.

Aqueous stability and degradation of psychiatric and neuroactive compounds and its biological activity in Daphnia magna

“…As it has been described in other target organisms (Faria et al, 2019a(Faria et al, , 2019b, D. magna responses to repetitive light stimuli are biphasic. The response to light stimuli increases until a maximum response is reached, and then the response decreases due to habituation (Bedrossiantz et al, 2020).…”

Screening anti-predator behaviour in fish larvae exposed to environmental pollutants

“…In this regard, it is important to address if fish larvae survival can be compromised by exposure to such pollutants at realistic concentrations and also address the possibility to use automated and easily implemented methods with highthroughput potential to test a broad array of known and unknown neurotoxic pollutants present in the aquatic ecosystems. Recently we developed and validated the Vibrational Startle Response Assay (VSRA), an automated in vivo assay for identifying chemicals impairing the escape response and its habituation in zebrafish larvae (Faria et al, 2019a;Faria et al, 2019b). The assay is based on measuring the distance moved by the larva during the startle responses evoked by repetitive vibrational stimuli.…”

Short- and Long-Term Neurobehavioral Effects of the Developmental Exposure to Valproic Acid in Zebrafish

“…Interestingly, Gupta et al [25], in a seminal article on neuroanatomical mapping of the zebrafish brain, found that 6 dpf zebrafish larvae exposed to 50 M VPA during early development presented a loss of glutamatergic signal in part of the statoacoustic ganglion leading to a decreased acoustic startle responsiveness. Glutamate dysregulation is thought to be implicated in the changes of the startle response through NMDA and mGlu5 receptors [34][35][36][37].…”