Effects of cocaine on extracellular dopamine and serotonin levels in the nucleus accumbens

Psychopharmacology (Berl). 2001 May;155(3):221-9. doi: 10.1007/s002130100704.


Rationale: Although the rewarding effects of cocaine are generally attributed to its ability to increase dopamine (DA) transmission, cocaine demonstrates approximately equal affinity for dopamine and serotonin (5-HT) transporters in vitro. However, there have been few direct systematic comparisons of the effects of cocaine on DA and 5-HT transmission in vivo.

Objectives: The present experiments compared the effects of systemic cocaine administration, local cocaine infusion and the systemic administration of cocaine during infusion on extracellular levels of DA and 5-HT in the nucleus accumbens (NAc).

Methods: In vivo microdialysis in awake unrestrained rats was used to measure the effects of systemic administration and local infusion of cocaine on extracellular DA and 5-HT levels simultaneously in the NAc.

Results: Systemic cocaine (10-25 mg/kg, IP) dose-dependently increased DA and 5-HT levels, but the increase in DA was larger than for 5-HT at 18 mg/kg. Infusion of cocaine (0.1-10.0 mM) into the NAc increased both DA and 5-HT levels, but the effect on DA was larger than 5-HT at 0.1 and 3 mM cocaine. The influence of cocaine on DA and 5-HT somatodendritic autoreceptors was examined when cocaine (25 mg/kg) was administered systemically during cocaine infusion. The increase in DA and 5-HT levels during cocaine infusion was attenuated by the systemic injection of cocaine during cocaine infusion, but the decrease of 5-HT was greater than that for DA.

Conclusions: Cocaine produced a larger impact on DA than 5-HT neurotransmission under specific conditions. A series of physiological mechanisms, i.e. terminal density, neurotransmitter interactions and somatodendritic regulation, are discussed as factors responsible for facilitating cocaine's effects on DA relative to 5-HT.

Publication types

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

MeSH terms

  • Animals
  • Autoreceptors / drug effects
  • Cocaine / pharmacology*
  • Dopamine / metabolism*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • In Vitro Techniques
  • Male
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / metabolism*


  • Autoreceptors
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Cocaine
  • Dopamine