Single or repeated administrations of SCH 23390 fail to affect serotonergic neurotransmission

In synaptic membrane preparations from the frontal cortex of rats treated with single or repeated administration of mianserin or methysergide (10 mg/kg i.p.) the number of 5-HT2 receptors was reduced. In contrast, single (0.1 mg/kg or 5 mg/kg i.p.) or repeated administration of SCH 23390 (0.05 mg/kg i.p. twice daily for 3 weeks) failed to change the kinetic characteristics of 5-HT2 receptors. Moreover, in several cerebral areas, 5-HT levels and turnover were not modified by any treatment. Although SCH 23390 has a high affinity for cerebral 5-HT2 receptors, and there are conflicting data on the antagonistic activity in the periphery, our data show that doses which selectively affect dopaminergic transmission are devoid of serotonergic effects.