The objective of the present study was to examine the involvement of serotonin 5-HT2 receptors within the rat nucleus accumbens (Acc) in the regulation of dopamine (DA) release using in vivo microdialysis, Perfusion with the 5-HT2 agonist (+)-1 -(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), at concentrations of 25-250 mu M, through microdialysis probes located in the posterior Acc increased extracellular DA levels to a maximum of 200% of baseline. DOI-induced increases in the extracellular levels of DA were Ca2+ dependent and were inhibited by co-perfusion with the 5-HT2 antagonist LY-53,857, DOI enhancement of the extracellular concentrations of DA was observed when probes were implanted in the Acc core and shell regions posterior to anteroposterior +1.2 mm from bregma, whereas a small reduction in the extracellular levels of DA was observed in the anterior Acc. There were no differences between core and shell subdivisions within either the anterior or the posterior Ace. These results suggest that activation of 5-HT2 receptors within the posterior, but not anterior, Ace stimulates DA release, indicating rostral-caudal differences in the interactions of 5-HT with DA systems in the Acc.