Department of Psychology, Centre of Behavioural and Health Sciences, University of Tartu, Tartu, Estonia.
Neuropsychobiology. 2011;64(2):110-22. doi: 10.1159/000325224. Epub 2011 Jun 21.
BACKGROUND/AIMS: Rats display persistent behavioural phenotypes of low (LE) versus high (HE) exploratory activity in the exploration box paradigm. LE rats that prefer passive coping strategies show differential dopaminergic activity in the striatum. The main hypothesis of this study was that chronic variable stress (CVS) would have a higher impact on LE rats.
Animals were submitted to a CVS regimen lasting 32 days that was followed by a behavioural test battery. The functional states of their dopamine D(1) and D(2) receptors were measured in the striatum and nucleus accumbens (NAcc). Cerebral oxidative metabolism was assessed via cytochrome c oxidase histochemistry in 65 brain regions.
CVS decreased weight gain, to a higher extent in LE rats, and lowered the sucrose preference after the first week, but habituation to the anhedonic effect had developed by the end of the experiment. CVS did not change the behavioural phenotypes initially assigned. No effect of stress on D(2) receptor function was found. Chronically stressed animals exhibited higher levels of social interaction and D(1) receptor-mediated cAMP accumulation in the NAcc, but not in the striatum. CVS was associated with higher oxidative metabolism levels in the anteroventral thalamus, median raphe nuclei and central periaqueductal grey matter. These changes after stress did not depend upon the exploratory phenotype.
This study revealed changes in brain biochemistry after habituation to CVS that might be implicated in successful adaptation to chronic stress.
背景/目的:大鼠在探索箱范式中表现出低(LE)与高(HE)探索性活动的持久行为表型。偏好被动应对策略的 LE 大鼠在纹状体中表现出不同的多巴胺能活性。本研究的主要假设是慢性可变应激(CVS)对 LE 大鼠的影响更大。
动物接受了为期 32 天的 CVS 处理方案,随后进行了行为测试。在纹状体和伏隔核(NAcc)中测量了其多巴胺 D(1)和 D(2)受体的功能状态。通过细胞色素 c 氧化酶组织化学在 65 个脑区评估了大脑氧化代谢。
CVS 降低了体重增加,LE 大鼠的体重增加幅度更大,并且在第一周后降低了蔗糖偏好,但到实验结束时,对快感缺失效应已经产生了适应。CVS 最初并未改变分配的行为表型。应激对 D(2)受体功能没有影响。慢性应激动物表现出更高水平的社交互动和 NAcc 中的 D(1)受体介导的 cAMP 积累,但纹状体中没有。CVS 与前腹侧丘脑、中缝核和中央导水管周围灰质中更高的氧化代谢水平相关。应激后的这些变化与探索性表型无关。
本研究揭示了对 CVS 适应后的大脑生物化学变化,这些变化可能与对慢性应激的成功适应有关。