Abstract: AIM: To investigate the changes of phospho-cAMP response element binding protein (p-CREB) and c-Fos in two brain regions of morphine-reactivated conditioned place preference (CPP) in rats. METHODS: Morphine was administered by subcutaneous injection at gradually increasing dose for 6 days to establish morphine CPP.From the 7th day, the rats were administered saline instead of morphine for 10 days to induce CPP extinction.The rats were given a single priming injection of morphine to reactivate the morphine CPP.The p-CREB and c-Fos were assayed with immunohistochemistry method in the phase of recurrence of CPP rekindled by morphine.RESULTS: Increasing dose of morphine conditioning for 6 days resulted in acquisition of CPP and morphine (4 mg/kg) reactivated CPP following 10 days drug free period. Compared with saline control, morphine-reactivated CPP elevated the expression of p-CREB and c-Fos in hippocampus and amygdala in rats (P< 0.05).CONCLUSION: p-CREB and c-Fos expression in hippocampus and amygdala may be involved in the mechanisms of recurrence of CPP.

Key words: morphine, conditioned place preference, hippocampus, amygdala, cAMP response element binding protein, c-Fos