The antipsychotic drug risperidone interacts with auto- and hetero-receptors regulating serotonin output in the rat frontal cortex

  title={The antipsychotic drug risperidone interacts with auto- and hetero-receptors regulating serotonin output in the rat frontal cortex},
  author={Peter Hertel and G. Nomikos and Torgny H. Svensson},

Receptor-mediated regulation of serotonin output in the rat dorsal raphe nucleus: effects of risperidone

The findings suggest a regulatory role of local 5-HT1B/D receptors on 5- HT efflux as well as cell firing in the DRN and indicate that risperidone may interfere with the regulation of5-HT availability in this area primarily via blockade of 5-ht1D receptors.

Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT1B autoreceptors: a microdialysis study in knockout mice

The present study shows that terminal 5- HT1B autoreceptors play a significant role in the regulation of 5-HT release in the prefrontal cortex.

An evaluation of the effect of NAS-181, a new selective 5-HT1B receptor antagonist, on extracellular 5-HT levels in rat frontal cortex

The results show that NAS-181 is a potent 5-HT1B receptor antagonist, and partial agonistic properties of these compounds are suggested.

5-HT1B receptors and serotonin function : microdialysis studies in rats and knockout mice

The studies in mice and rats described in this thesis clearly show that 5-HT1B autoreceptors limit the acute effects of local administration of a SSRI in the hippocampus and frontal cortex and an increased response to SSRIs may be expected.

Role of extracellular serotonin levels in the effect of 5-HT1B receptor blockade

The results provide circumstantial evidence that the effect of a 5-HT1B receptor antagonist depends on extracellular 5- HT levels, but strongly suggest that additional5-HT reuptake inhibition is required to detect any effect of 5-ht1B cannabinoid receptor antagonist on 4-HT levels by in vivo microdialysis.

Adjunctive alpha2-adrenoceptor blockade enhances the antipsychotic-like effect of risperidone and facilitates cortical dopaminergic and glutamatergic, NMDA receptor-mediated transmission.

It is proposed that the therapeutic effect of risperidone in schizophrenia can be enhanced and its extrapyramidal side-effect liability reduced by adjunctive treatment with an alpha2-adrenoceptor antagonist, and generally support the notion that the potent alpha1-adRenoceptor antagonistic action of clozapine may be highly important for its unique efficacy in schizophrenia.

A Novel Approach to the Identification of Psychiatric Drugs: Serotonin-Glutamate Interactions in the Prefrontal Cortex

It is suggested that elucidation of the specific receptors that suppress glutamate release induced by 5-HT2A receptor activation in the medial prefrontal cortex may lead to novel therapeutic targets for depression, such as metabotropic glutamate agonists which may not be efficacious in screening strategies primarily dependent on synaptic availability of monoaminergic neurotransmitters.

Distinct electrophysiological effects of paliperidone and risperidone on the firing activity of rat serotonin and norepinephrine neurons

The capacity of paliperidone to reverse the selective serotonin reuptake inhibitor (SSRI)-induced inhibition of NE neuronal firing, without interfering with the effect of SSRIs of 5-HT neuronal activity, suggests that palipersidone may be a very effective adjunct in SSRI-resistant depression.



Serotonin-mediated increase in prefrontal cortex dopamine release: pharmacological characterization.

A functional interaction between DA and 5- HT pathways in the PFC is demonstrated, with evidence of potential mediation by the 5-HT1B receptor subtype.

Risperidone inhibits 5‐hydroxytryptaminergic neuronal activity in the dorsal raphe nucleus by local release of 5‐hydroxytryptamine

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.

In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat brain areas differentially innervated by the dorsal and median raphe nuclei

The present data suggest that the comparable effects of SSRIs in DRN- and MRN-innervated forebrain regions are not explained by a preferential attenuation of 5-HT release by terminal5-HT1B autoreceptors in hippocampus, an area with a low inhibitory influence of somatodendritic 5- HT1A receptors.

Serotonin, schizophrenia and antipsychotic drug action

  • A. Breier
  • Psychology, Medicine
    Schizophrenia Research
  • 1995

Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly in addition 5-HT1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex

The results confirm the view that the serotonin axons of rat brain possess 5-HT1B autoreceptors, and give additional credence to previous suggestions that, in the rabbit and guinea-pig, the autoreCEPTors are 5- HT1D.

Potentiation of the Fluoxetine‐Induced Increase in Dialysate Levels of Serotonin (5‐HT) in the Frontal Cortex of Freely Moving Rats by Combined Blockade of 5‐HT1A and 5‐HT1B Receptors with WAY 100,635 and GR 127,935

5‐HT1A/1B antagonism may represent a novel strategy for the improvement in the therapeutic profile of 5‐ HT reuptake inhibitor antidepressant agents and that 5‐HT may be primarily involved in such interactions.