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

Rationale: Although the rewarding effects of cocaine are generally attribut ed to its ability to increase dopamine (DA) transmission, cocaine demonstra tes approximately equal affinity for dopamine and serotonin (5-HT) transpor ters in vitro. However, there have been few direct systematic comparisons o f the effects of cocaine on DA and 5-HT transmission in vivo. Objectives: T he present experiments compared the effects of systemic cocaine administrat ion, local cocaine infusion and the systemic administration of cocaine duri ng 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 coc aine on extracellular DA and 5-HT levels simultaneously in the NAc. Results : Systemic cocaine (10-25 mg/kg, IF) dose-dependently increased DA and 5-HT levels, but the increase in DA was larger than for 5-HT at is mg/kg. Infus ion 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 in fluence of cocaine on DA and 5-HT somatodendritic autoreceptors was examine d when cocaine (25 mg/kg) was administered systemically during cocaine infu sion. The increase in DA and 5-HT levels during cocaine infusion was attenu ated by the systemic injection of cocaine during cocaine infusion, but the decrease of 5-HT was greater than that for DA. Conclusions: Cocaine produce d a larger impact on DA than 5-HT neurotransmission under specific conditio ns. A series of physiological mechanisms, i.e. terminal density, neurotrans mitter interactions and somatodendritic regulation, are discussed as factor s responsible for facilitating cocaine's effects on DA relative to 5-HT.