We have previously shown with a model of morphine-induced conditioned place preference (CPP) that a brief exposure to footshock stress or a priming dose of morphine could reactivate drug-seeking behavior after a long drug-free period. The present study was designed to examine the possible role of certain brain areas in such a reactivation. After the rats were successfully trained with morphine (4 mg/kg, i.p.) through a CPP paradigm (10 sessions of daily pairing of morphine with one of the two compartments), different parts of nucleus accumbens (NAc), ventral tegmental area (VTA), and central (Ce) or lateral (La) nucleus of amygdala were lesioned with a DC current passing through the respective location. After a 9-day abstinence period, random intermittent footshock (DC square wave, 0.5 mA, 0.5 s width, off time 10-70 s) or drug priming (morphine 0.25 mg/kg, s.c.) reactivated the place preference in sham lesion rats. However, the effect of drug priming could be completely abolished by lesions placed either at VTA, or the majority or shell part, but not the core of NAc. On the other hand, the effect of footshock stressor could be eliminated by a lesion placed at Ce but not La. These results suggest that, while both drug priming and footshock stress are effective in reactivating drug-seeking behavior, they might work through different neurochemical mechanisms and anatomical pathways.