Serotonin-dependent cerebral activation: effects of methiothepin and other serotonergic antagonists

In scopolamine-treated (5.0 mg/kg, s.c.) rats hippocampal rhythmical slow activity (RSA) and neocortical low voltage fast activity (LVFA) occur only in close correlation with head movements, spontaneous changes in posture, or locomotion (Type I behavior). Previous work indicates that such scopolamine-resistant RSA and LVFA are dependent on ascending serotonergic projections. A test of 9 serotonergic antagonists (methiothepin; ritanserin; ketanserin; pizotifen; mianserin; pirenperone; ICS-205-930; metoclopramide; methysergide) showed that methiothepin produces a partial reduction in RSA and LVFA in scopolamine-treated rats, while the other antagonists are completely inactive over a wide range of doses. It may be that serotonergic cerebral activation depends on both 5-HT1 and 5-HT2 receptors.