• C M Andrews and I Lucki.
• Institute of Neurological Sciences, University of Pennsylvania, Philadelphia 19104, USA.
• Psychopharmacology (Berl.). 2001 May 1;155(3):221-9.

RationaleAlthough 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.ObjectivesThe 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).MethodsIn 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.ResultsSystemic 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.ConclusionsCocaine 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.

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