Agonist effects at putative central 5-HT4 receptors in rat hippocampus by R(+)- and S(-)-zacopride; no evidence for stereo-selectivity.

The EEG of halothane anaesthetized rats was recorded from an electrode implanted into the hippocampus. In the present study the effect of R(+)- and S(-)-zacopride, administered intra-cerebroventricularly, on different frequency bands of the EEG was investigated. Both enantiomers induced similar dose-dependent (5-20 micrograms) increases in all frequency bands. The effects of R(+)- and S(-)-zacopride were inhibited by pretreatment with a high dose of ICS 205-930 (1 micrograms i.c.v.), which suggests the involvement of 5-HT4 receptors. The lack of stereo-selectivity of the zacopride enantiomers is in contrast to observations made in in vitro studies.