Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: disruption by cocaine sensitization

Neuron. 2005 Jul 21;47(2):255-66. doi: 10.1016/j.neuron.2005.06.017.


The prefrontal cortex and the hippocampus exhibit converging projections to the nucleus accumbens and have functional reciprocal connections via indirect pathways. As a result, information processing between these structures is likely to be bidirectional. Using evoked potential measures, we examined the interactions of these inputs on synaptic plasticity within the accumbens. Our results show that the direction of information flow between the prefrontal cortex and limbic structures determines the synaptic plasticity that these inputs exhibit within the accumbens. Moreover, this synaptic plasticity at hippocampal and prefrontal inputs selectively involves dopamine D1 and D2 activation or inactivation, respectively. Repeated cocaine administration disrupted this synaptic plasticity at hippocampal and prefrontal cortical inputs and goal-directed behavior in the spatial maze task. Thus, interactions of limbic-prefrontal cortical synaptic plasticity and its dysfunction within the accumbens could underlie complex information processing deficits observed in individuals following psychostimulant administration.

Publication types

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

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Amphetamine / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage*
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Evoked Potentials / radiation effects
  • Limbic System / drug effects
  • Limbic System / physiology*
  • Limbic System / radiation effects
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Models, Biological
  • Neuronal Plasticity / drug effects*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Prefrontal Cortex / radiation effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Amphetamine
  • Cocaine
  • Dopamine