Figure 3.

Illustrates the mechanisms that contribute to less (or blunted) amphetamine-induced dopamine release in cocaine abusers (Panels C and D) relative to healthy controls (Panels A and B). Cocaine abusers (Panel C) have [1] fewer vesicular monoamine transporters [2] comparable number of dopamine transporters and [3] fewer dopamine D_2/3 receptors relative to healthy controls (Panel A) at baseline. Following, an acute amphetamine challenge (the red arrows show the mechanisms by which amphetamine releases dopamine via reverse transport at the dopamine transporter and depletion of the vesicular dopamine stores) less dopamine is released in cocaine abusers (Panel D) relative to healthy controls (Panel B), which may be due to a reduction in the number of pre-synaptic dopamine storage vesicles (chronic cocaine-induced adaptation) and/or terminals (chronic cocaine-induced toxicity). It is possible that either or both these possibilities is reflected as lower VMAT2 binding in cocaine abusers relative to healthy controls as observed in this study.