Stereotypic behaviour in the deer mouse: pharmacological validation and relevance for obsessive compulsive disorder.
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.
Korff
Schaun
S
Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University (Potchefstroom Campus), Potchefstroom, 2520, South Africa.
Stein
Dan J
DJ
Harvey
Brian H
BH
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D010542:Peromyscus; D010879:Piperazines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology / Q000627:therapeutic use*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; D018491:Dopamine Agonists; D005473:Fluoxetine; D010879:Piperazines; D019257:Quinpirole; D017448:Receptors, Dopamine D2; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C113776:dopamine D2L receptor; C015068:1-(3-chlorophenyl)piperazine