Background and Methods:
Serotonin-1A (5-HT1A) receptors have been implicated in the symptoms of schizophrenia. However, there is limited in vivo evidence for an interaction of antipsychotic drugs with 5-HT1A receptor-mediated behavioural effects. We therefore investigated in rats the action of several antipsychotic drugs on prepulse inhibition (PPI), a measure of sensorimotor gating, which is deficient in schizophrenia. Disruption of PPI was induced by treatment with 0.5 mg/kg of the 5-HT1A receptor agonist, 8-hydroxy-di-propyl-aminotetralin (8-OH-DPAT).
Results:
In rats pretreated with 0.25 mg/kg of haloperidol or raclopride, the disruption of PPI was no longer significant. Of the atypical antipsychotic drugs clozapine, olanzapine, risperidone, amisulpride and aripiprazole, only aripiprazole significantly reduced the effect of 8-OH-DPAT on PPI. This effect was mimicked by pretreatment with the 5-HT1A receptor partial agonist, buspirone. On the other hand, some of the antipsychotic drugs and other pretreat-ments showed complex, prepulse-dependent effects on their own, both on PPI and prepulse facilitation at the 30 ms ISI (clozapine, risperidone, amisulpride) and PPI at the 100 ms ISI (olanzapine, risperidone, MDL 73,005 EF).
Conclusions:
These data show little in vivo interaction of several atypical antipsychotic drugs with the disruption of PPI mediated by 5-HT1A receptor stimulation. The action of haloperidol and raclopride suggests a major involvement of dopamine D2 receptors in this effect, possibly downstream from the initial se-rotonergic stimulation. The action of aripiprazole could be mediated by its partial agonist properties at 5-HT1A receptors or its dopamine D2 blocking properties.
