期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 32, 期 2, 页码 348-355出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2007.08.032
关键词
deer mouse; desipramine; fluoxetine; obsessive compulsive disorder; pharmacological validation; stereotypy
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.
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