We have previously shown that chronic treatment with the partial mu-opioid receptor agonist, buprenorphine, blocks the nucleus accumbens dopamine response to an acute injection of heroin, whereas it potentiates the response to an acute injection of cocaine after 4-5 days of treatment. Here we studied the effects of chronic exposure to buprenorphine via osmotic minipumps for up to 28 days (1.5 or 3.0 mg/kg/day) on responses to acute injections of heroin and cocaine. Increases in locomotion induced by heroin (0.25 mg/kg, sc), given on the 5th, 15th or 25th day of treatment were unaffected by buprenorphine, whereas increases induced by cocaine (20 mg/kg, ip) were enhanced early in treatment but not on the 15th or 25th days. Using in vivo microdialysis we found that both the suppression of the dopaminergic response in the nucleus accumbens to heroin and the potentiation to cocaine seen early in treatment diminished over the 26-27 days, whereas basal dopamine levels remained elevated throughout. Therefore, although these studies do not explain the mechanism whereby buprenorphine reduces heroin and cocaine intake, they do indicate that there is little tolerance to the presence of chronic buprenorphine. © 2006 Elsevier Inc. All rights reserved.