Neuronal substrates of relapse to cocaine-seeking behavior: role of prefrontal cortex

J Exp Anal Behav. 2005 Nov;84(3):653-66. doi: 10.1901/jeab.2005.105-04.


The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cocaine / administration & dosage
  • Cocaine / adverse effects
  • Cocaine-Related Disorders / physiopathology*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Dopamine / physiology
  • Electroencephalography / drug effects
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Feedback / physiology
  • Glutamic Acid / physiology
  • Male
  • Motivation*
  • Nerve Net / drug effects
  • Nerve Net / physiopathology
  • Neurons / drug effects
  • Neurons / physiology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Self Administration
  • Substance Withdrawal Syndrome / physiopathology


  • Glutamic Acid
  • Cocaine
  • Dopamine