Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University (Potchefstroom Campus), Hofman street, Potchefstroom, 2520, South Africa.
Physiol Behav. 2011 Jun 1;103(3-4):404-11. doi: 10.1016/j.physbeh.2011.03.008. Epub 2011 Mar 21.
The deer mouse presents with spontaneous stereotypic movements that resemble the repetitive behaviours of obsessive-compulsive disorder (OCD), and demonstrates a selective response to serotonin reuptake inhibitors. OCD has been linked to altered redox status and since increased dopamine signalling can promote stereotypies as well as oxidative stress, we investigated whether the severity of deer mouse stereotypy may be associated with altered dopamine turnover and cortico-striatal redox status. Deer mice were separated into high (HSB), low (LSB) and non-stereotypy (NS) groups. Frontal cortical and striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as superoxide dismutase (SOD) activity, reduced (GSH) and oxidised (GSSG) glutathione and glutathione redox index, were analysed as markers for regional dopamine turnover and oxidative stress, respectively. Dopamine and its metabolites and SOD activity did not differ across the stereotypy groups. Significantly reduced GSH and GSSG and increased glutathione redox index were only observed in the frontal cortex of HSB animals. Frontal cortical GSH and GSSG were inversely correlated while glutathione redox index was positively correlated with stereotypy. Deer mouse stereotypy is thus characterised by a deficient glutathione system in the frontal cortex but not striatum, and provides a therapeutic rationale for using glutathione-active antioxidants in OCD. The evidence for a primary frontal lesion has importance for future OCD research.
自发性刻板运动的鹿鼠表现出类似于强迫症（OCD）的重复行为，并且对 5-羟色胺再摄取抑制剂表现出选择性反应。OCD 与氧化还原状态改变有关，并且由于多巴胺信号增加可以促进刻板行为和氧化应激，我们研究了鹿鼠刻板行为的严重程度是否与多巴胺周转率和皮质纹状体氧化还原状态的改变有关。将鹿鼠分为高刻板组（HSB）、低刻板组（LSB）和非刻板组（NS）。分析额皮质和纹状体多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）以及超氧化物歧化酶（SOD）活性、还原型（GSH）和氧化型（GSSG）谷胱甘肽以及谷胱甘肽氧化还原指数，分别作为区域多巴胺周转率和氧化应激的标志物。刻板组之间多巴胺及其代谢物和 SOD 活性没有差异。仅在 HSB 动物的额皮质中观察到 GSH 和 GSSG 显著减少以及谷胱甘肽氧化还原指数增加。额皮质中的 GSH 和 GSSG 呈负相关，而谷胱甘肽氧化还原指数与刻板行为呈正相关。因此，鹿鼠刻板行为的特征是额皮质而不是纹状体中的谷胱甘肽系统不足，并为使用谷胱甘肽活性抗氧化剂治疗 OCD 提供了治疗依据。原发性额损伤的证据对未来的 OCD 研究具有重要意义。
