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The hindering effects of metals and in particular lead (Pb) are representing a growing threat to aquatic organisms such as fish. This observation derives from toxic concentrations of Pbaccounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host-cleaning symbiosis. In this study, the nominal PbNO3 concentration of 1.6 mg/L was capable of reducing feeding and resting bouts asearly as 24 h of exposure while hyperactive swimming episodes were also detected. Such abnormal behaviors were tightly correlated to up-regulated orexin receptor (ORXR) mRNA expression levels in some brain areas such as the lateral thalamic nucleus (+213%) and the optictectum (+90%) with respect to controls. Interestingly, these transcriptional effects seemed to be attenuated when Pb-exposed fish received either 100 ng/g of ORX-A (-70%) or 0.1 μg/g of γ-aminobutyric acidA receptor (GABAAR) agonist muscimol (MUS; -97%) compared to fish exposed to Pb alone. Moreover, a net neurodegenerative process of the different brain areas wasreported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only. Conversely,addition of the GABAAR antagonist bicuculline (BIC; 1 μg/g) moderately (p<0.05) enhanced Pb-dependent behavioral and neurodegenerative actions. Overall, these first indications stronglypoint to altered ORXR/GABAAR interactions during neurotoxic events of a metal that byevoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health.

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