Transition to addiction is associated with a persistent impairment in synaptic plasticity

Science. 2010 Jun 25;328(5986):1709-12. doi: 10.1126/science.1187801.

Abstract

Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive*
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / physiopathology*
  • Disease Models, Animal
  • Glutamic Acid / metabolism
  • Long-Term Synaptic Depression*
  • Nucleus Accumbens / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Self Administration
  • Synaptic Transmission

Substances

  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Glutamic Acid
  • Cocaine