Schedule‐Induced Polydipsia: A Rat Model of Obsessive‐Compulsive Disorder

Brian Platt1, Chad E. Beyer1, Lee E. Schechter1, Sharon Rosenzweig‐Lipson1

1 Wyeth Research, Princeton, New Jersey
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.27
DOI:  10.1002/0471142301.ns0927s43
Online Posting Date:  April, 2008
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Abstract

Obsessive‐compulsive disorder (OCD) is difficult to model in animals due to the involvement of both mental (obsessions) and physical (compulsions) symptoms. Due to limitations of using animals to evaluate obsessions, OCD models are limited to evaluation of the compulsive and repetitive behaviors of animals. Of these, models of adjunctive behaviors offer the most value in regard to predicting efficacy of anti‐OCD drugs in the clinic. Adjunctive behaviors are those that are maintained indirectly by the variables that control another behavior, rather than directly by their own typical controlling variables. Schedule‐induced polydipsia (SIP) is an adjunctive model in which rats exhibit exaggerated drinking behavior (polydipsia) when presented with food pellets under a fixed‐time schedule. The polydipsic response is an excessive manifestation of a normal behavior (drinking), providing face validity to the model. Furthermore, clinically effective drugs for the treatment of OCD decrease SIP. This protocol describes a rat SIP model of OCD and provides preclinical data for drugs that decrease polydipsia and are clinically effective in the treatment of OCD. Curr. Protoc. Neurosci. 43:9.27.1‐9.27.8. © 2008 by John Wiley & Sons, Inc.

Keywords: obsessive‐compulsive disorder; polydipsia; adjunctive drinking; in vivo; rat

     
 
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Table of Contents

  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1:

  Materials
  • Male rats, single housed
  • Food pellets (45 mg dustless precision pellets, Bio‐Serv, no. F0021)
  • Saline
  • Drug of interest
  • Standard rat operant chamber (Skinner box) including the following (from Med Associates):
    • ENV‐007 (Extra Tall Modular Operant Test Chamber with waste pan, dual wall)
    • ENV‐005 (Stainless Steel Grid Floor—standard rat)
    • ENV‐215M (House Light, hooded, 100 mA, 28V DC)
    • ENV‐225SM (White Noise Amplifier with Cage Speaker)
    • ENV‐203M (Modular Pellet Dispenser)
    • ENV‐200R2M (Pellet Receptacle, Trough type)
  • Sound‐attenuating cubicle (e.g., Extra Tall Expanded PVC Sound Attenuating Cubicle; Med Associates, EVN‐018V)
  • Interface cabinet (Med Associates) including:
    • SG‐6510D (Large Table Top Interface Cabinet with 28 Volt DC Supply for up to 16 Chambers)
    • DIG‐716P2 (SmartCtrl 8 Input 16 Output Package)
    • DIG‐700P2 (PCI Interface Connection Package)
  • 100‐ml graduated bottle fitted with rubber stopper and curved drinking tube
  • Plastic clasps
  • Animal scale
  • Computer equipped with MedPC software (Med Associates)
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Figures

Videos

Literature Cited

Literature Cited
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   Falk, J.L. 1971. The nature and determinants of adjunctive behavior. Physiol. Behav. 6: 577‐588.
   Hogg, S. and Dalvi, A. 2004. Acceleration of onset of action in schedule‐induced polydipsia: Combinations of SSRI and 5‐HT1A and 5‐HT1B receptor antagonists. Pharmacol. Biochem. Behav. 77: 69‐75.
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   Palfai, T., Kutscher, C.L., and Symons, J.P. 1971. Schedule‐induced polydipsia in the mouse. Physiol. Behav. 6: 461‐462.
   Pitman, R.K. 1989. Animal models of compulsive behavior. Biol. Psychiatry 26: 189‐198.
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   Weissman, M.M., Bland, R.C., Canino, G.J., Greenwald, S., Hwu, H., Lee, C.K., Newman, S.C., Oakley‐Browne, M.A., Rubio‐Stipec, M.R., Wickramaratne, P.J., Wittchen, H., and Yeh, E. 1994. The cross national epidemiology of obsessive compulsive disorder. J. Clin. Psychiatry 55: 5‐10.
   Woods, A., Smith, C., Szewczak, M., Dunn, R.W., Cornfeldt, M., and Corbett, R. 1993. Selective serotonin re‐uptake inhibitors decrease schedule‐induced polydipsia in rats: A potential model for obsessive compulsive disorder. Psychopharmacology 112: 195‐198.
   Woods‐Kettelberger, A., Kongsamut, S., Smith, C.P., Winslow, J.T., and Corbett, R. 1997. Animal models with potential applications for screening compounds for the treatment of obsessive‐compulsive disorder. Exp. Opin. Invest. Drugs 6: 1369‐1381.
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