Insights to drug addiction derived from ultrastructural views of the mesocorticolimbic system

Drugs of abuse increase the release of dopamine from mesocorticolimbic neurons in the ventral tegmental area. Thus, insights into the cytoarchitecture and the synaptic circuitry affecting the activity of dopaminergic neurons in this area are fundamental for understanding the commonalities produced by mechanistically distinct drugs of abuse. Electron microscopic immunolabeling has provided these insights and also shown the critical relationships between the dopaminergic axon terminals and their targeted neurons in the prefrontal cortex and in the both the dorsal and ventral striatum. These brain regions are among those where dopamine and associated neurotransmitters are most implicated in the transition from recreational to compulsive consumption of reinforcing drugs. Thus, the synaptic circuitry and drug-induced plasticity occurring in the ventral tegmental area and in dopamine-targeted regions are reviewed, as both are essential for understanding the long-lasting changes produced by addictive substances.