5-HT4 receptor modulation of acetylcholine outflow in guinea pig brain slices.

The effect of the 5-HT4 agonist, BIMU-8 was studied on [3H]choline outflow in guinea pig brain slices and synaptosomes. BIMU-8 did not modify [3H]choline efflux in slices kept at rest, but increased [3H]choline outflow in electrically stimulated slices of cerebral cortex (CC), hippocampus (hip) and nucleus basalis magnocellularis (nbm). This effect was prevented by the selective 5-HT4 antagonist, GR 125487. Conversely, BIMU-8 did not affect [3H]choline efflux in hippocampal synaptosomes depolarized with KCl 20 mM. These results provide evidence that BIMU-8 increases the electrically triggered [3H]choline efflux in CC, hip and nbm slices. A possible role of 5-HT4 agonists in memory and learning diseases is suggested.