What he could not envision 2,500 years ago was that, at the end of the 20th century, advanced technologies would produce drugs that mimic all the sensations that the brain produces endogenously. The first part of Hippocrates' quotation refers to the initial state of drug use, when sensations are positive and incentive builds to use again. The second part of the quote corresponds to the second, third, and final stages of drug use-addiction, withdrawal, and craving. This presentation focuses on the initial phase and the initial targets of cocaine in the brain. Accumulating evidence indicates that dopamine-containing neurons are principal targets of cocaine in the brain.
Dopamine is found in neurons unevenly distributed in the brain.
At least four major clusters of cells produce dopamine. Of these, the mesolimbic dopamine neurons are often implicated as the mediators of reward or reinforcement. They originate in the ventral tegmental area and project to various forebrain structures, including the nucleus accumbens and cortical regions. When dopamine is released from these projection neurons, it activates at least five subtypes of presynaptic and postsynaptic dopamine receptors. In these regions, a single dose of cocaine raises the extracellular concentration of dopamine, and the rise and decline of dopamine correspond temporally to the cocaine levels in the blood and brain.