Tolerance-like attenuation to contingent and noncontingent cocaine-induced elevation of extracellular dopamine in the ventral striatum following 7 days of withdrawal from chronic treatment

Psychopharmacology (Berl). 1995 Apr;118(3):338-46. doi: 10.1007/BF02245964.


Time-dependent changes in mesolimbic dopamine (DA) function are believed to play a role in behavioral sensitization and drug craving experienced during withdrawal from chronic cocaine administration. The present study utilized intravenous (IV) cocaine self-administration coupled with intracranial microdialysis in rats to investigate time dependent changes during withdrawal from chronic cocaine exposure. Following 2 weeks of IV cocaine self-administration, rats were allowed contingent access to cocaine at 1 and 7 days of withdrawal while extracellular levels of DA were measured from the ventral striatum. A second group of animals received yoked, noncontingent cocaine for 2 weeks and were then administered noncontingent cocaine on days 1 and 7 of withdrawal. In addition, a third group of animals received 2 weeks of yoked saline followed by noncontingent cocaine 1 day after withdrawal. There were no significant differences between groups for the overall cocaine dosage or temporal pattern of infusions on days 1 and 7 of withdrawal. Basal extracellular DA concentrations did not differ between any treatment groups at either withdrawal time. Extracellular DA levels were increased throughout the session on both days; however, the increases at day 7 were significantly less than day 1 for both contingent and noncontingent conditions. DA overflow on day 1 did not differ between animals receiving chronic yoked cocaine or saline. These results suggest that tolerance-like attenuation to the DA-elevating effects of cocaine is not apparent early in withdrawal, but does develop by later time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects
  • Corpus Striatum / drug effects*
  • Dopamine / metabolism*
  • Drug Tolerance
  • Male
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration*
  • Substance Withdrawal Syndrome / etiology
  • Time Factors


  • Cocaine
  • Dopamine