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

被引:77
作者
Korff, Schaun [1 ]
Stein, Dan J. [2 ]
Harvey, Brian H. [1 ]
机构
[1] NW Univ, Sch Pharm Pharmacol, Unit Drug Res & Dev, ZA-2520 Potchefstroom, South Africa
[2] Univ Cape Town, Dept Psychiat & Mental Hlth, MRC Unit Anxiety & Stress Disorders, ZA-7925 Cape Town, South Africa
基金
新加坡国家研究基金会; 英国医学研究理事会;
关键词
deer mouse; desipramine; fluoxetine; obsessive compulsive disorder; pharmacological validation; stereotypy;
D O I
10.1016/j.pnpbp.2007.08.032
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 x21 days). We also studied behavioural responses to the 5-HT2A/C agonist, meta-chlorophenylpiperazine (mCPP) and the D-2 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-HT2A/C and dopamine D-2 receptor agonists. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:348 / 355
页数:8
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