Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum

Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC. Intrastriatal administration of 1 mM or 5 mM TMX has not produced significant increases on dopamine (DA) levels, nonetheless the infusion of 10 mM TMX increases the DA output to 841 ± 132%, when compared to basal levels. Infusion of 1 mM CLO has not induced a significant increase in DA levels, even so 2, 3.5 and 5 mM CLO have produced an increase of 438 ± 8%, 2778 ± 598% and 4604 ± 516%, respectively, every compared to basal levels. Mecamylamine (MEC), a non-competitive nAChRs antagonist, was used to investigate the role of nAChRs on DA release induced by TMX and CLO. The increases in extracellular DA levels induced by TMX and CLO when associated to MEC are 80% and 68% lower than the effect produced by CLO and TMX isolated. These results confirm that TMX and CLO appear to induce in vivo DA increased release in striatum of rats and it seems to be concentration dependent. Moreover, these results indicate that this effect might be related to nAChRs.