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Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition

Psychopharmacology volume 180, pages 366–376 (2005)Cite this article

Abstract

Rationale

Schizophrenia has been linked to dysregulation of dopamine and glutamate transmitter systems. Attempts to model aspects of schizophrenia in animals have made use of treatments that primarily affect dopaminergic (e.g., amphetamine, Amp) and glutamatergic (e.g., phencyclidine, PCP) function. In addition to exerting short-term acute effects, these agents also induce long-term effects, as seen, for example, in neurochemical and behavioural sensitization.

Objectives

The goal of this work was to compare Amp- and PCP-sensitized states on two measures of information processing that are impaired in schizophrenia, prepulse inhibition (PPI) of the acoustic startle reflex and latent inhibition (LI).

Methods

Rats received injections of Amp, PCP or saline 3 days per week for 3 weeks. The Amp dose increased from 1 to 3 mg/kg, at the rate of 1 mg/kg each week. The PCP dose was 3 mg/kg throughout. After various periods of withdrawal rats were tested for PPI and LI.

Results

Repeated intermittent treatment with Amp or PCP resulted in augmented locomotor responses to challenge with each drug, providing an operational index that sensitization had occurred. Rats sensitized to Amp showed disrupted PPI when tested drug free at 3, 21 and 60 days of withdrawal. Amp-sensitized rats also showed abolition of the LI effect. Rats sensitized to PCP did not show deficits in any of these behaviours when tested drug free.

Conclusions

Because disrupted PPI and LI have both been reported in schizophrenic patients, these results suggest that the Amp-sensitized state may represent a useful model for investigating the neural bases of information processing deficits in schizophrenia.

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Acknowledgements

This work was supported by a special initiative grant from the Ontario Mental Health Foundation (OMHF). C.T. was supported by a Research Fellowship from the OMHF. S.K. is supported by a Canadian Research Chair in Schizophrenia and Therapeutic Neuroscience.

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Author notes

  1. Catherine C. Tenn

    Present address: DRDC Suffield, P.O. Box 4000, Station Main, Medicine Hat, Alberta, T1A 8K6, Canada

Affiliations

  1. Schizophrenia/PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Catherine C. Tenn & Shitij Kapur

  2. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Shitij Kapur & Paul J. Fletcher

  3. Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Paul J. Fletcher

  4. Biopsychology Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada

    Paul J. Fletcher

Authors
  1. Catherine C. Tenn
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  2. Shitij Kapur
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  3. Paul J. Fletcher
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Correspondence to Paul J. Fletcher.

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Tenn, C.C., Kapur, S. & Fletcher, P.J. Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition. Psychopharmacology 180, 366–376 (2005). https://doi.org/10.1007/s00213-005-2253-z

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Keywords

  • Amphetamine
  • Phencyclidine
  • Prepulse inhibition
  • Latent inhibition
  • Schizophrenia
  • Sensitization