The role of serotonin receptor subtypes in the behavioural effects of neuroleptic drugs. A paw test study in rats.

The present study was designed to evaluate the roles of serotonin 5-HT1A and 5-HT2 receptors in the effects of neuroleptic drugs in the paw test. This behavioural test has been shown to model both the antipsychotic efficacy as well as the extrapyramidal side-effect liability of neuroleptic drugs. Whereas the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) reduced the effects of the classical neuroleptic haloperidol, it increased the effects of the atypical neuroleptic clozapine. The 5-HT2 receptor antagonist ketanserin as well as the 5-HT1C/5-HT2 receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) reduced the effects of clozapine. The most important finding, however, was that the behavioural effects of different (putative) neuroleptics (fluphenazine, SCH-39166, remoxipride, prothipendyl, thioridazine and risperidone) were differentially influenced by both 8-OHDPAT and DOI, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subclasses of classical and atypical neuroleptics.