Figure 7.

Effects of termination of MAM treatment on rolipram-induced changes in hippocampal neurogenesis and expression of pCREB and CREB in the mouse hippocampus and prefrontal cortex. (a) Confocal micrographs of BrdU-labeled cells (green) in the dentate gyrus from mice, which had been repeatedly treated with vehicle (Veh), MAM, rolipram (Rol), MAM + rolipram, with a 3-week washout of MAM. (b) Quantification of BrdU-positive cells following the drug treatments. Rolipram-induced increases in BrdU-positive cells were no longer inhibited by MAM 3 weeks after termination of its treatment. (c and d) Rolipram-induced increases in pCREB in the hippocampus (c) and prefrontal cortex (d) were not changed after termination of MAM treatment; the treatments did not alter expression of CREB. Lower panels are representative immunoblots of pCREB or CREB detected by Western blotting; upper panels are quantification of pCREB and CREB. Rolipram (1.25 mg/kg) was given (i.p.) for 37 d and MAM (5 mg/kg) was co-administered (s.c.) with rolipram or vehicle for the first 14 d. BrdU (100 mg/kg) was injected (i.p.) once per day on days 24, 26, and 28. Mice were perfused or sacrificed 1 h after the final injection of rolipram or vehicle on day 37. Values shown are means ± S.E.M of 4−5 mice per group. * p < 0.05, ** p < 0.01 vs Veh + Sal; # p < 0.05, ## p < 0.01 vs MAM + Veh.