Neurochemical changes in cocaine withdrawal

Trends Pharmacol Sci. 1996 Jul;17(7):260-4. doi: 10.1016/0165-6147(96)10024-9.


Cocaine withdrawal in animals causes a transient increase followed by a long-lasting decrease in mesolimbic dopamine transporters, dopamine efflux and the number of dopamine cells firing spontaneously. Other changes in the nucleus accumbens and frontal cortex also suggest alterations in dopamine-receptive neurones and circuits. In humans, brain imaging has provided evidence for some similar, long-lasting changes in dopaminergic neurones and innervated areas. These results suggest a protracted biochemical abstinence syndrome for cocaine. In this review, Michael Kuhar and Nancy Pilotte focus on biochemical changes that occur following withdrawal from repeated cocaine administration. A key question for treatment is whether (some of) these persistent changes underlie withdrawal symptomatology such as anhedonia and relapse.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Chemistry
  • Cocaine / adverse effects*
  • Cocaine / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Drug Design
  • Frontal Lobe / cytology
  • Frontal Lobe / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • Neurons / cytology
  • Neurons / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / metabolism*
  • Substance Withdrawal Syndrome / metabolism*
  • Synapses / metabolism


  • Cocaine
  • Dopamine