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Strain differences in the neurochemical response to chronic restraint stress in the rat: relevance to depression.

机译:对大鼠慢性束缚应激的神经化学反应中的应变差异:与抑郁症的相关性。

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The neurochemical basis of depression focuses on alterations in the monoaminergic and amino acid neurotransmitter systems. Moreover, decreases in serum levels of the neurotrophin brain-derived neurotrophic factor (BDNF) have led to the more recent neurotrophic hypothesis of depression. Chronic stress is one of the major predisposing factors to developing the disorder and thus we investigated the impact of chronic restraint stress on the levels of several neurotransmitters and their metabolites in a genetic animal model of depression, the Wistar Kyoto (WKY) rat. Behavioural analysis of WKY rats indicated both a depressive and anxiety-like phenotype compared to their Sprague Dawley (SD) controls. WKY animals showed similar stress-induced decreases in hippocampal GABA, noradrenaline and dopamine as their SD counterparts while exhibiting a divergent decrease in 5-HT, 5-HIAA and DOPAC. WKY rats also showed a stress-dependent increase in GABA concentrations in the amygdala compared to the SD animals. Moreover, WKY but not SD rats had a chronic stress-induced decrease in serum BDNF levels. Together these data show that there are specific strain-dependent changes in neurotransmitter and neurotrophin levels in response to chronic stress which may predispose WKY animals to a depressive-like phenotype.
机译:抑郁症的神经化学基础集中于单胺能和氨基酸神经递质系统的改变。此外,神经营养蛋白脑源性神经营养因子(BDNF)血清水平的降低导致了抑郁症的最新神经营养学假说。慢性应激是导致该疾病的主要诱因之一,因此,我们在患有抑郁症的遗传动物模型Wistar Kyoto(WKY)大鼠中研究了慢性束缚应激对几种神经递质及其代谢产物水平的影响。 WKY大鼠的行为分析表明,与Sprague Dawley(SD)对照相比,它具有抑郁和焦虑样的表型。 WKY动物表现出与SD对应物相似的应激诱导的海马GABA,去甲肾上腺素和多巴胺下降,而5-HT,5-HIAA和DOPAC则表现出不同的下降。与SD动物相比,WKY大鼠在杏仁核中的GABA浓度也显示出应力依赖性增加。此外,WKY而非SD大鼠具有慢性应激诱导的血清BDNF水平降低。这些数据加在一起表明,响应慢性应激,神经递质和神经营养蛋白水平存在特定的应变依赖性变化,这可能使WKY动物容易出现抑郁样表型。

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