Synergic effect of prucalopride with donepezil on sAPPα secretion in the hippocampus (a and b) and cortex (c and d) of wild-type mice. An inactive dose of the selective acetylcholine esterase inhibitor, donepezil (0.75 mg kg−1, s.c.), was administered 30 min after prucalopride. This combination induced a synergic increase in sAPPα levels in the hippocampus and cortex. The hippocampus and cortex were removed 90 min after prucalopride injection and Western-blot analysis was performed to determine sAPPα levels. In (a and c) representative immunoblots illustrating the effects of different treatments (S=saline, P=prucalopride, 5 mg kg−1, D=donepezil, 0.75 mg kg−1) on sAPPα levels are shown. In (b and d), the mean densitometric values (±s.e.m.) of sAPPα levels, relative to β-actin (used as internal control), are expressed as percentages of values in untreated control mice (clear bar). One-way ANOVA, for P only vs P+D, in hippocampus, F(3,9)=27.28; in cortex, F(3,14)=10.03. **P<0.01 and ***P<0.001 compared with saline-treated mice. #P<0.01 and ###P<0.001 compared with prucalopride-treated mice; least significant difference test; n=4–6 mice per group.