Triadimefon triggers circling behavior and conditioned place preference/aversion in zebrafish in a dose dependent manner

Triadimefon (TDF) is a pesticide used in agricultural crops to control powdery mildews, rusts and other fungal pests. It exerts its fungicidal activity through the inhibition of ergosterol biosynthesis, impairing the formation of the cell membrane. For vertebrates, one of its side effects is the binding to the dopamine transporter increasing the levels of synaptic dopamine, similarly to cocaine. In addition, it has been demonstrated that TDF affects the abundance of other monoamines in the brain, specifically serotonin. It is well known that drugs which alter the dopaminergic and serotonergic systems produce behavioral changes and participate in the development of addictions in mammals. In this work we have used the conditioned place preference paradigm to assess, for the first time, the rewarding properties of TDF in zebrafish. We found out that TDF triggers both, preference and aversion depending on the dosage used during conditioning. We observed that 5 mg/L produced aversion to the pattern previously paired with TDF. However, 15 mg/L induced the opposite behavior, showing that zebrafish seek out those environments which had previously been paired with the higher dose of TDF. These results are congruent with our previous findings, where we showed that 5 mg/L reduced the levels of serotonin, usually linked to anxious behaviors (a negative cue), whereas higher concentrations of TDF increased extracellular dopamine, the main currency of the reward system. Interestingly, both doses of TDF induced circling behavior, a feature usually seen in glutamatergic antagonists.