Stereotypic behaviour in the deer mouse: pharmacological validation and relevance for obsessive compulsive disorder

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):348-55. doi: 10.1016/j.pnpbp.2007.08.032. Epub 2007 Aug 29.

Abstract

Stereotypy is an important manifestation of obsessive compulsive disorder (OCD). OCD involves disturbed serotonin and dopamine pathways, and demonstrates a selective response to serotonin reuptake inhibitors (SRI), with limited to no response to noradrenaline reuptake inhibitors (NRI). Deer mice (Peromyscus maniculatus bairdii) engage in various spontaneous stereotypic behaviours, including somersaulting, jumping and pattern running, and has to date not been explored for possible relevance for OCD. We studied the population diversity of spontaneous stereotypy in these animals, followed by assessing behavioural response to chronic high and low dose SRI (viz. fluoxetine) and NRI (viz. desipramine) treatment (both 10 mg/kg; 20 mg/kg x 21 days). We also studied behavioural responses to the 5-HT(2A/C) agonist, meta-chlorophenylpiperazine (mCPP) and the D2 agonist, quinpirole (2 mg/kg and 5 mg/kg respectively x 4 days). Deer mice showed a distinct separation into high and low stereotypic behaviour populations, with high and low dose fluoxetine, but not desipramine, significantly reducing stereotypic behaviour in both populations. A significant attenuation of stereotypy was also observed in both groups following quinpirole or mCPP challenge. In its response to drug treatment, spontaneous stereotypic behaviour in deer mice demonstrates predictive validity for OCD. States of spontaneous stereotypy are attenuated by 5-HT(2A/C) and dopamine D2 receptor agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Desipramine / pharmacology
  • Desipramine / therapeutic use*
  • Disease Models, Animal*
  • Dopamine Agonists / pharmacology
  • Dopamine Agonists / therapeutic use*
  • Drug Evaluation, Preclinical
  • Female
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / psychology
  • Peromyscus
  • Piperazines / pharmacology
  • Quinpirole / pharmacology
  • Quinpirole / therapeutic use*
  • Receptors, Dopamine D2 / agonists*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / pharmacology
  • Species Specificity
  • Stereotyped Behavior / drug effects*
  • Stereotyped Behavior / physiology

Substances

  • Antidepressive Agents, Tricyclic
  • Dopamine Agonists
  • Piperazines
  • Receptors, Dopamine D2
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • dopamine D2L receptor
  • Fluoxetine
  • Quinpirole
  • 1-(3-chlorophenyl)piperazine
  • Desipramine