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Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia

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Abstract

Rationale

The ketamine (ket) model reflects features of schizophrenia as well as secondary symptoms such as altered pain sensitivity.

Objectives

In the present study, we investigated the effect of subchronic oral treatment with haloperidol (hal, 0.075 mg/kg) and risperidone (ris, 0.2 mg/kg) on altered pain perception and locomotor activity in this model.

Results

In reaction to 5 mg/kg morphine, ket pretreated animals showed a diminished analgesic response. Hal had no analgesic effect per se, but the compound normalised the analgesic reaction to morphine in the ket pretreated animals. The effect of ris was complex. First, there was no analgesic effect per se, and control animals showed a dose-dependent increase in the analgesic index after morphine injection. In the ket group treated with ris, the analgesic response to 5 mg/kg morphine was attenuated and in response to 10 mg/kg analgesia was comparable with that measured in controls. The reduced analgesic effect was not due to pharmacokinetic differences in morphine metabolism. After administration via drinking water in saline-injected control animals, the hal blood serum concentration was 2.6 ± 0.45 ng/ml. In ket-injected animals, the mean serum concentration of hal amounted to 1.2 ± 0.44 ng/ml. In the experiment using ris, animals in the control group had higher ris serum concentrations compared with ket-injected animals. In control animals, morphine dose dependently decreased locomotor activity. This effect was significantly stronger in the ket pretreated groups.

Conclusions

Hal and ris had different effects on altered pain sensitivity. It was hypothesised that these results are connected with alterations in dopamine D2 and μ opioid receptor binding.

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Acknowledgements

The professional technical assistance of Petra Dehmel, Doreen Heidemann, Sandra Heller, Beate Reuter, and Gabriele Schulze is gratefully acknowledged. This study was supported by the Bundesministerium für Bildung und Forschung (NBL3).

Disclosure/conflict of interest

The authors have no financial interests to disclose.

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Authors and Affiliations

  1. Faculty of Medicine, Institute of Pharmacology and Toxicology, Otto von Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

    Axel Becker & Gisela Grecksch

  2. Experimental Psychiatry Unit, Department of Psychiatry, Medical University Innsbruck, Innrain 66 a, Innsbruck, 6020, Austria

    Gerald Zernig & Elisabeth Ladstaetter

  3. Department of Psychiatry, Johannes Gutenberg University, Untere Zahlbacher Str. 8, 55101, Mainz, Germany

    Christoph Hiemke & Ulrich Schmitt

Authors
  1. Axel Becker
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  2. Gisela Grecksch
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  4. Elisabeth Ladstaetter
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  5. Christoph Hiemke
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Correspondence to Axel Becker.

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Becker, A., Grecksch, G., Zernig, G. et al. Haloperidol and risperidone have specific effects on altered pain sensitivity in the ketamine model of schizophrenia. Psychopharmacology 202, 579–587 (2009). https://doi.org/10.1007/s00213-008-1336-z

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  • DOI: https://doi.org/10.1007/s00213-008-1336-z

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