The effects of antipsychotic drugs on serotonergic activity in the rat hippocampus.
The serotonergic activity in hippocampus was investigated following acute and chronic treatment with the antipsychotic drugs haloperidol and risperidone. Acute administration of risperidone, the serotonin(2) (5-HT(2)) receptor antagonist ketanserin, and the dopamine (DA)-D(2) receptor antagonist raclopride increased the 5-hydroxyindoleacetic acid/serotonin (5-HIAA/5-HT) ratio. In contrast, acute administration of haloperidol did not affect this ratio. Chronic administration of risperidone maintained the increased 5-HIAA/5-HT ratio; a challenge dose of risperidone after the chronic treatment and the subsequent washout period also maintained the increased ratio. Chronic administration of haloperidol as well as a challenge dose of haloperidol following chronic treatment did not affect the serotonergic activity in hippocampus. Administration of ketanserin or raclopride after chronic treatment and the washout period induced an additional increase in the 5-HIAA/5-HT ratio in risperidone-treated rats. Moreover, a challenge dose of ketanserin, but not raclopride, increased the 5-HIAA/5-HT ratio in haloperidol-treated rats. The present results indicate that acute and chronic treatment of haloperidol or risperidone modified serotonergic activity in the hippocampus in a different way. Moreover, the augmentation of serotonergic activity induced by risperidone did not seem to be solely related to dopaminergic or serotonergic properties and may be of particular relevance for the amelioration of schizophrenia symptoms.