Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine

Eur J Neurosci. 1999 May;11(5):1598-604. doi: 10.1046/j.1460-9568.1999.00576.x.


Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug-induced neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity, allowed access to a running wheel. They were then left undisturbed for 24-25 days before their brains were processed for Golgi-Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex. Cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Behavior, Animal / physiology
  • Cell Size / physiology
  • Cocaine / pharmacology*
  • Dendrites / drug effects*
  • Dendrites / ultrastructure
  • Dopamine Uptake Inhibitors / pharmacology*
  • Female
  • Nucleus Accumbens / cytology*
  • Prefrontal Cortex / cytology*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / ultrastructure
  • Rats
  • Rats, Sprague-Dawley


  • Dopamine Uptake Inhibitors
  • Amphetamine
  • Cocaine