Reactive oxygen species modulate locomotor activity and dopamine extracellular levels induced by amphetamine in rats

The increase of dopamine (DA) in the reward system is related to the reinforcing effects of drugs of abuse and hyper locomotion induced by psychostimulants. The increase of DA induced by drugs of abuse generates high amounts of ROS by monoamines metabolization. It has been showed that ROS could modulate psychomotor response and reinforcing effects induced by drugs of abuse as cocaine and methamphetamine (METH). The aim of this study is to evaluate the relation of ROS and amphetamine (AMPH). Here, we show that pretreatment of the ROS scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) attenuates the induction of locomotion and oxidative stress generated in nucleus accumbens (Nac) by acute AMPH administration. Interestingly, TEMPOL also attenuates the increase of DA induced by AMPH in Nac. Finally, TEMPOL reduces DAT phosphorylation when AMPH is co-infused in Nac synaptosomes. Taking together, our results suggest that ROS modulate AMPH effects in rats.