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

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Abstract

Rationale

Paliperidone (9-OH-risperidone) is the main metabolite of the atypical antipsychotic risperidone. While both drugs are potent dopamine (D)2 antagonists, they have quantitative differential affinities for serotonin (5-HT) and norepinephrine (NE) receptor binding sites.

Objectives

The present study aimed to determine if paliperidone exerts distinct effects on 5-HT and NE neuronal activity from those of risperidone.

Materials and methods

Risperidone and paliperidone were administered to Sprague–Dawley rats. Neuronal activity of 5-HT and NE neurons was assessed using in vivo electrophysiology.

Results

Acute administration of risperidone but not paliperidone inhibited the firing of 5-HT neurons, as previously reported. This inhibition was partially antagonized by the NE reuptake inhibitor desipramine, by the 5-HT1A receptor antagonist WAY 100635, and completely reversed when both drugs were given consecutively. Risperidone inhibited the firing of 5-HT neurons after 2 and 14 days of administration, with or without escitalopram. Paliperidone did not alter the firing rate of NE neurons by itself, but it reversed the suppression of NE neurons induced by escitalopram, as it was previously reported for risperidone.

Conclusion

These results indicate that although risperidone and paliperidone share a qualitatively similar receptor binding profile in vitro, they differentially alter the firing of 5-HT and NE neurons in vivo. 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 paliperidone may be a very effective adjunct in SSRI-resistant depression.

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Acknowledgments

This research was supported by Janssen Pharmaceuticals. PB received a Canada Research Chair in Psychopharmacology and an Endowed Chair from the University of Ottawa Institute of Mental Health Research. ED received a postdoctoral fellowship from Bar-Ilan University (Israel). We thank Dr. Owen Kelly for his help with statistical analyses and Lundbeck A/S for supplying escitalopram.

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Authors and Affiliations

  1. University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue Suite 6419, Ottawa, ON, K1Z-7K4, Canada

    Eliyahu Dremencov, Mostafa El Mansari & Pierre Blier

  2. Department of Psychiatry, University of Ottawa, Ottawa, Canada

    Pierre Blier

  3. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada

    Pierre Blier

Authors
  1. Eliyahu Dremencov
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  2. Mostafa El Mansari
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  3. Pierre Blier
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Correspondence to Eliyahu Dremencov.

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Dremencov, E., El Mansari, M. & Blier, P. Distinct electrophysiological effects of paliperidone and risperidone on the firing activity of rat serotonin and norepinephrine neurons. Psychopharmacology 194, 63–72 (2007). https://doi.org/10.1007/s00213-007-0818-8

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  • DOI: https://doi.org/10.1007/s00213-007-0818-8

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