An investigation into the presynaptic actions by which amphetamine activates dopamine signaling within striatal subregions of the rat.

Despite decades of intense research and a consensus view in the field, the work presented herein provides strong evidence that the primary mechanism of amphetamine action should be re-evaluated. Rather than depleting vesicular dopamine stores and promoting non-exocytotic efflux through the dopamine transporter in vivo, recent evidence demonstrates that amphetamine augments phasic dopamine signaling instead. This signaling modality is critical for reinforcement learning and is dependent on intact vesicular stores. The new findings support over-activation of phasic dopamine signaling as a common mechanism in the addiction process