Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use

Biol Psychiatry. 2005 Nov 1;58(9):751-9. doi: 10.1016/j.biopsych.2005.04.046. Epub 2005 Aug 11.


Background: Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction.

Methods: Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies.

Results: When re-exposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex).

Conclusions: The transition from stable to escalated cocaine use, a hallmark of addiction, is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Cocaine / administration & dosage*
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / psychology
  • Conditioning, Operant / drug effects
  • Dendrites / drug effects
  • Dendrites / ultrastructure
  • Dose-Response Relationship, Drug
  • Head Movements / drug effects
  • Male
  • Motor Activity / drug effects
  • Neuronal Plasticity / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology
  • Nucleus Accumbens / ultrastructure
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology
  • Prefrontal Cortex / ultrastructure
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology
  • Self Administration
  • Stereotyped Behavior / drug effects


  • Cocaine