Reduced clearance of exogenous dopamine in rat nucleus accumbens, but not in dorsal striatum, following cocaine challenge in rats withdrawn from repeated cocaine administration

J Neurochem. 1993 Jul;61(1):273-83. doi: 10.1111/j.1471-4159.1993.tb03565.x.


We investigated whether changes in the dopamine transporter in the nucleus accumbens or striatum are involved in cocaine-induced behavioral sensitization by using in vivo electrochemistry to monitor the clearance of locally applied dopamine in anesthetized rats. Rats were injected with cocaine-HCl (10 mg/kg i.p.) or saline daily for 7 consecutive days and then withdrawn for 7 days. Pressure ejection of a finite amount of dopamine at 5-min intervals from a micropipette adjacent to the electrochemical recording electrode produced transient and reproducible dopamine signals. After a challenge injection of cocaine (10 mg/kg i.p.), the signals in the nucleus accumbens of cocaine-treated animals became prolonged and the clearance rate of the dopamine decreased, indicating significant inhibition of the dopamine transporter. In contrast, simultaneous measurements in the dorsal striatum indicated a transient increase in both the amplitude of the signals and the clearance rate of the dopamine. The signals in both brain regions in the saline-treated animals given the cocaine challenge were similar to those in untreated animals given an acute injection of cocaine (10 mg/kg i.p.) or saline. Behaviorally, not all of the cocaine-treated animals were sensitized; however, both sensitized and nonsensitized animals displayed similar changes in dopamine clearance rate. Quantitative autoradiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine and the density of binding sites were similar in cocaine- and saline-treated rats. The decrease in dopamine clearance rate observed in the nucleus accumbens of the cocaine-treated rats after a challenge injection of cocaine is consistent with increased dopaminergic transmission, but does not appear to be sufficient in itself for producing behavioral sensitization.

Publication types

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

MeSH terms

  • Animals
  • Autoradiography
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage
  • Cocaine / pharmacology*
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Antagonists
  • Electrochemistry
  • Male
  • Mazindol / metabolism
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Substance Withdrawal Syndrome / metabolism*


  • Dopamine Antagonists
  • Mazindol
  • Cocaine
  • Dopamine