Figure 1. Effects of cocaine and amphetamine on the dopamine transporter.

(A) Under normal conditions, dopamine neuron firing results in dopamine-filled vesicles to fuse with the presynaptic membrane and subsequently dopamine is released into the synaptic cleft. Once in the synapse dopamine can bind to post-synaptic dopamine receptors and then is removed from extracellular space by the dopamine transporter (DAT). Once dopamine is back inside the presynaptic terminal, it is repackaged into synaptic vesicles for future release via the vesicular monoamine transporter (VMAT). (B) Cocaine increases levels of dopamine by binding to the DAT and thereby inhibiting dopamine uptake back into the terminal. As dopamine uptake is reduced, levels accumulate in the synapse and dopamine has a greater opportunity to bind to dopamine receptors. (C) Amphetamines increase the synaptic concentration of dopamine through two main mechanisms. Amphetamines interfere with the reuptake of dopamine through the DAT, and they disrupt vesicular packaging of dopamine which increases cytosolic levels of dopamine which can then leak out through the DAT via reverse transport.