Models of Aspects of Schizophrenia: Behavioral Sensitization Induced by Subchronic Phencyclidine Administration

Mikhail Kalinichev1, Simon T. Bate2, Declan N.C. Jones3

1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, United Kingdom, 2 Statistical Sciences, GlaxoSmithKline, Harlow, Essex, United Kingdom, 3 Centre of Excellence for External Drug Discovery, GlaxoSmithKline, Harlow, Essex, United Kingdom
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.54
DOI:  10.1002/0471141755.ph0554s45
Online Posting Date:  June, 2009
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Presented in this unit is a protocol using subchronically administered phencyclidine (PCP) for establishing a behavioral sensitization model of aspects of schizophrenia. This model is validated using haloperidol and risperidone. The end‐point of the assay is locomotor hyperactivity, which is induced by PCP challenge following subchronic treatment with this NMDA receptor antagonist. The antipsychotics haloperidol, risperidone, and quetiapine all reduce hyperactivity in a dose‐dependent and selective manner. While the effects of other antipsychotics such as clozapine, olanzapine, and ziprasidone are similar to haloperidol, the interpretation of responses to them is often confounded by nonspecific effects during habituation. Curr. Protoc. Pharmacol. 45:5.54.1‐5.54.13. © 2009 by John Wiley & Sons, Inc.

Keywords: phencyclidine; sensitization; animal model; hyperactivity; haloperidol; risperidone; antipsychotic drugs

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Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: Behavioral Sensitization in the Rat Following Sub‐Chronic Phencyclidine (PCP) Administration
  • Basic Protocol 2: Testing a Compound for Aspects of Schizophrenia Based on Phencyclidine Administration
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Basic Protocol 1: Behavioral Sensitization in the Rat Following Sub‐Chronic Phencyclidine (PCP) Administration

  • Adult male Sprague‐Dawley rats (200 to 250 g; 11 to 12 animals per group)
  • Rat food (Harlan Tekland 2014, Harlan UK)
  • Test compound solution(s) (e.g., phencyclidine hydrochloride, saline; see recipe)
  • Rat housing
  • Apparatus for measuring locomotor activity (see )

Basic Protocol 2: Testing a Compound for Aspects of Schizophrenia Based on Phencyclidine Administration

  • Test compound solution(s) (e.g., phencyclidine hydrochloride, haloperidol, risperidone; see recipe)
  • Adult male Sprague‐Dawley rats (200 to 250 g)
  • Vehicles, e.g., saline, water, 1% methylcellulose
  • Apparatus for measuring locomotor activity (see )
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Literature Cited

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