AbstractThe present study was designed to evaluate the roles of serotonin 5‐HT1Aand 5‐HT2receptors 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‐HT1Areceptor 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‐HT2receptor antagonist ketanserin as well as the 5‐HT1C/5‐HT2receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5‐HT1C/5‐HT2receptor agonist 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOl) 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 DOl, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subc