How addictive drugs disrupt presynaptic dopamine neurotransmission

Neuron. 2011 Feb 24;69(4):628-49. doi: 10.1016/j.neuron.2011.02.010.


The fundamental principle that unites addictive drugs appears to be that each enhances synaptic dopamine by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. This occurs via the modulation of synaptic mechanisms that can be involved in learning, including enhanced excitation or disinhibition of dopamine neuron activity, blockade of dopamine reuptake, and altering the state of the presynaptic terminal to enhance evoked over basal transmission. Amphetamines offer an exception to such modulation in that they combine multiple effects to produce nonexocytic stimulation-independent release of neurotransmitter via reverse transport independent from normal presynaptic function. Questions about the molecular actions of addictive drugs, prominently including the actions of alcohol and solvents, remain unresolved, but their ability to co-opt normal presynaptic functions helps to explain why treatment for addiction has been challenging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamines / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Central Nervous System Agents / pharmacology*
  • Cocaine / pharmacology
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Ethanol / pharmacology
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Models, Biological
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects
  • Nicotine / pharmacology
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / physiology
  • Synaptic Transmission / drug effects*


  • Amphetamines
  • Analgesics, Opioid
  • Central Nervous System Agents
  • Hypnotics and Sedatives
  • Ethanol
  • Nicotine
  • Cocaine
  • Dopamine