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

Ann N Y Acad Sci. 2012 Feb;1248:71-88. doi: 10.1111/j.1749-6632.2011.06299.x. Epub 2011 Dec 16.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / ultrastructure
  • Humans
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Limbic System / physiopathology*
  • Limbic System / ultrastructure
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Mesencephalon / physiopathology*
  • Mesencephalon / ultrastructure
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Nucleus Accumbens / ultrastructure
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology*
  • Prefrontal Cortex / ultrastructure
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / pathology
  • Substance-Related Disorders / physiopathology*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology
  • Ventral Tegmental Area / ultrastructure