• Neuroleptic drugs;
  • spontaneous firing;
  • 5-hydroxytryptamine;
  • dorsal raphe nucleus;
  • electrophysiology;
  • microdialysis
  • 1
    The effects of risperidone on brain 5-hydroxytryptamine (5-HT) neuronal functions were investigated and compared with other antipsychotic drugs and selective receptor antagonists by use of single cell recording and microdialysis in the dorsal raphe nucleus (DRN).
  • 2
    Administration of risperidone (25–400 μg kg−1, i.v.) dose-dependently decreased 5-HT cell firing in the DRN, similar to the antipsychotic drug clozapine (0.25–4.0 mg kg−1, i.v.), the putative antipsychotic drug amperozide (0.5–8.0 mg kg−1, i.v.) and the selective α1-adrenoceptor antagonist prazosin (50–400 μg kg−1, i.v.).
  • 3
    The selective α2-adrenoceptor antagonist idazoxan (10–80 μg kg−1, i.v.), in contrast, increased the firing rate of 5-HT neurones in the DRN, whereas the D2 and 5-HT2A receptor antagonists raclopride (25–200 μg kg−1, i.v.) and MDL 100,907 (50–400 μg kg−1, i.v.), respectively, were without effect. Thus, the α1-adrenoceptor antagonistic action of the antipsychotic drugs might, at least partly, cause the decrease in DRN 5-HT cell firing.
  • 4
    Pretreatment with the selective 5-HT1A receptor antagonist WAY 100,635 (5.0 μg kg−1, i.v.), a drug previously shown to antagonize effectively the inhibition of 5-HT cells induced by risperidone, failed to prevent the prazosin-induced decrease in 5-HT cell firing. This finding argues against the notion that α1-adrenoceptor antagonism is the sole mechanism underlying the inhibitory effect of risperidone on the DRN cells.
  • 5
    The inhibitory effect of risperidone on 5-HT cell firing in the DRN was significantly attenuated in rats pretreated with the 5-HT depletor PCPA (p-chlorophenylalanine; 300 mg kg−1, i.p., day−1 for 3 consecutive days) in comparison with drug naive animals.
  • 6
    Administration of risperidone (2.0 mg kg−1, s.c.) significantly enhanced 5-HT output in the DRN.
  • 7
    Consequently, the reduction in 5-HT cell firing by risperidone appears to be related to increased availability of 5-HT in the somatodendritic region of the neurones leading to an enhanced 5-HT1A autoreceptor activation and, in turn, to inhibition of firing, and is probably only to a minor extent caused by its α1-adrenoceptor antagonistic action.