The mechanisms of the antidepressant action of the oligosaccharides (P-6) extracted from Morinda Officinalis were studied. By flow cytometry analysis, treatment of PC12 cells with corticosterone (Cort) induced apoptosis in a concentration and time dependent manner. The highest percentage of apoptotic cells accumulated to 27.85 +/- 9.2% following pretreatment with Cort 10 muM for 5 d. In agarose gel electrophoresis of DNA, the sample obtained from PC12 cells pretreated with Cort 10 muM for 5 d showed a typical ladder pattern suggesting that Cort increased the DNA fragmentation significantly. Furthermore, the ultrastructure of Cort-treated cells displayed typical apoptosis-like morphological changes including fragmented chromatin accumulation to the inside of nucleolus membrane with a shape like crescent moon or ring, nuclear fragmentation or apoptotic body. In the presence Of P-6, or tricyclic antidepressant desipramine (DIM), the apoptosis induced by Cort in the three measurements above was significantly, inhibited. These results indicate that DIM or P-6 antagonize the apoptosis induced by Cort in PC12 cells, which may be one of the cellular mechanisms of their antidepressant effects. (C) 2002 Published by Elsevier Science Inc.