The nucleus accumbens has been subdivided into a shell and a core compartment on the basis of histochemical and connectional differences. Recently, we reported that behavioral sensitization to morphine is associated with an increased dopamine transmission in the caudate-putamen and in the nucleus accumbens core as well as a decreased response in the nucleus accumbens shell following acute morphine challenge. We have now performed a similar study in rats sensitized to amphetamine and to cocaine. Behavioral sensitization was induced by daily administration of a single dose of 1 mg/kg s.c. of amphetamine for 10 days or of 10 mg/kg i.p. of cocaine twice a day for 14 days. Microdialysis was performed 10-14 days after the last injection of amphetamine and 7-10 days after the last injection of cocaine. Both schedules resulted in robust behavioral sensitization in response to challenge with 0.25 and 0.5 mg/kg of amphetamine and to 5 and 10 mg/kg of cocaine, respectively. Subjects pre-exposed to amphetamine showed a sensitization of dopamine transmission in the nucleus accumbens core but not in the nucleus accumbens shell. Subjects pre-exposed to cocaine showed sensitization of dopamine transmission in the core only to the lower dose of cocaine. In the shell no change was observed after the lower dose of cocaine while a significant reduction of the dopamine response was observed after the higher dose. These results suggest that behavioral sensitization might result from reciprocal changes in the response of nucleus accumbens dopamine in the shell and in the core to drug challenge