The Role of Serotonin Receptor Subtypes in the Behavioural Effects of Neuroleptic Drugs. A Paw Test Study in Rats

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Abstract
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 (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 subclasses of classical and atypical neuroleptics.