Zacopride and BRL 24924 induce an increase in EEG-energy in rats

1. The substituted benzamides, zacopride and BRL 24924 induced dose-dependent increases of the total EEG-energy of rats when applied intracerebroventricularly (i.c.v.) with ED50 values of 8.0 +/- 0.6 and 3.6 +/- 0.9 micrograms, respectively. Not only the energy of the low frequency hippocampal theta rhythm but also that of the other frequency bands was increased. 2. In contrast to i.c.v. application intraperitoneal administration of zacopride or BRL 24924 (1 and 10 mg kg-1) did not lead to an increase in EEG-energy. 3. The increase in EEG-energy induced by zacopride (10 micrograms, i.c.v.) was blocked by ICS 205-930 (1 microgram, i.c.v.). Neither the 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine (30 micrograms, i.c.v.) nor the selective 5-HT3 receptor antagonist MDL 72222 (30 micrograms, i.c.v.) had any effect upon rat EEG. 4. Scopolamine (0.01 micrograms and 0.1 micrograms, i.c.v.) dose-dependently antagonized the effect of zacopride (10 micrograms, i.c.v.). 5. An agonist action of zacopride and BRL 24924 and inhibition of these effects by ICS 205-930 but not by MDL 72222 was recently described in isolated colliculi neurones from neonatal mice. The receptor involved was described as '5-HT4'. The present results indicate that the central effects of zacopride and BRL 24924 may be due to activation of such a 5-HT receptor.