Neurobehavioral effects of copper are related to a differentiated prepro-orexin synthesis in the Ornate wrasse

Copper (Cu) is an essential metal that becomes very toxic at high concentrations especially for aquatic vertebrates. Although Cu-dependent respiratory disturbances are well-recognized in fish, little is known about its role as neurotoxicant. The aim of the present study was to assess Cu effects on the behavioral performances of a marine teleost (Thalassoma pavo) that was exposed to sub-lethal (SL; 0.25 mg/L) or Maximum Acceptable Toxicant (MAT; 1.07 mg/L) concentrations of CuCl2 for 48 h. Interestingly, the latter concentration accounted for a great reduction (p<0.01) of feeding behaviors while only a moderate reduction (p<0.05) was detected during SL exposure. At the same time, MAT concentration of Cu was responsible for a very great increase (p<0.001) in abnormal motor activities such as erratic swimming plus rapid and abrupt movements. After the entire treatment session, some animals were kept in Cu-free water for another 48 h in order to evaluate their capacity to recover from toxicant-induced stress. In this additional period only fish exposed to SL concentrations restored normal swimming performances and eating stimuli. Surprisingly, at the brain level RT-PCR analysis displayed a great down-regulation of prepro-orexin mRNA especially after exposure to higher Cu concentrations (-64%), while mRNA levels were restored following a 48 h permanence in Cu-free water in fish previously treated with SL concentrations. These results tend to underlie an inhibitory role of Cu on both feeding and motor performances probably via impairments of ORXergic neuronal mechanisms thus suggesting that Cu neurotoxicity may be preferentially directed towards hypothalamic circuits.