Models for Assessing Antipsychotics: Antagonism of Amphetamine‐Induced Hyperactivity and Stereotypies in Mice

Sylvain Roux1, Anne‐Marie Hay1, Ruger D. Porsolt1

1 Phoenix International Pharmacology, Le Kremlin‐Bicêtre Cedex, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.17
DOI:  10.1002/0471141755.ph0517s04
Online Posting Date:  May, 2001
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All classical antipsychotics, such as chlorpromazine and haloperidol, have potent dopamine receptor‐blocking properties

This unit describes the rat anti‐Thy‐1.1 model of acute proliferative glomerulonephritis for the study of chronic renal insufficiency. A procedure is detailed for the induction of glomerulonephritis in rats as well as measurement of daily urinary excretion of protein, which is a convenient, primary screening tool. The unit also provides methods for assessment of glomerular filtration rate and effective renal plasma flow in anesthetized rats with anti‐Thy‐1.1‐induced renal insufficiency.

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Table of Contents

  • Basic Protocol 1: Antagonism of Amphetamine‐Induced Hyperactivity in Mice
  • Basic Protocol 2: Antagonism of Amphetamine‐Induced Stereotypies in Mice
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Antagonism of Amphetamine‐Induced Hyperactivity in Mice

  • 20‐ to 25‐g male NMRI (Naval Medical Research Institute) mice (e.g., Centre d'Elevage Roger Janvier [CERJ])
  • Test compound solutions (see recipe) and vehicle
  • D‐Amphetamine sulfate (Sigma) in physiological saline (0.9% NaCl; dose expressed as mg/kg of sulfate salt)
  • Physiological saline
  • 25 × 19 × 13–cm macrolon cages with wood shavings, food, and water
  • Animal balance, accuracy 0.1 g (e.g., Sartorius 1401‐001)
  • 1‐ml syringes
  • 25‐G 5/8‐in. (0.5 × 16–mm) needles (for intraperitoneal administration)
  • 23‐G × 1‐in. (0.6 × 25–mm) needles (for subcutaneous administration)
  • 25 × 12–mm Luer gastric probes with olive extremity (for oral administration)
  • 20 × 10 × 10–cm Plexiglas boxes containing wood shavings
  • Test apparatus: 24 covered Plexiglas cages (9 cm high × 21 cm wide × 26 cm long) each equipped with two crisscross photocell assemblies, contained within a darkened enclosure and connected to a computer that conducts the experiment and collects data (e.g., Orgasystem, Loval, France)
  • Holding cage for animals that have been tested

Basic Protocol 2: Antagonism of Amphetamine‐Induced Stereotypies in Mice

  • Test apparatus: individual Plexiglas cages (4 cm high × 7 cm wide ×11 cm long) attached with the opening against a 120 × 74–cm vertical grid containing a maximum of 48 cages (e.g., Orgasystem, Loval, France)
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Literature Cited

Literature Cited
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   Carlsson, A. 1988. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1:179‐186.
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   Lyon, M. 1991. Animal models with parallels to schizophrenia. In Neuromethods Vol 18: Animal Models in Psychiatry (A. Boulton, G. Baker, and M. Martin‐Iverson eds.) pp 25‐65. Humana Press, London.
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