Osterlund M K, Overstreet D H, Hurd Y L
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, S-171 76, Stockholm, Sweden.
Brain Res Mol Brain Res. 1999 Dec 10;74(1-2):158-66. doi: 10.1016/s0169-328x(99)00274-0.
The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.
利用一种抑郁症的基因动物模型——弗林德斯敏感系（FSL）大鼠，与对照的弗林德斯抗性系大鼠相比，研究了雌激素与血清素（5-羟色胺，5-HT）在抑郁症中的可能联系。分析了用17β-雌二醇（0.15微克/克）或赋形剂处理的去卵巢FSL和FRL大鼠几个边缘系统相关区域中雌激素受体（ER）α和β亚型以及5-HT（1A）和5-HT（2A）受体的mRNA水平。结果显示，FSL动物在嗅周皮质、梨状皮质和杏仁核内侧前背核中5-HT（2A）受体转录本的表达水平显著较低，而在海马体CA 2-3区域中表达水平较高。在ER mRNA表达方面，两系大鼠之间唯一的显著差异出现在杏仁核内侧后背核，FSL大鼠在该区域的ERα表达水平较低。总体而言，雌二醇处理使两系大鼠多个检测区域中的5-HT（2A）受体mRNA水平升高，5-HT（1A）受体mRNA水平降低。因此，在许多区域发现雌二醇调节5-HT受体mRNA表达的方向与FSL大鼠中发现的改变相反。这些发现进一步支持了5-HT受体，特别是5-HT（2A）亚型在情感障碍病因学中的作用。此外，雌二醇调节5-HT（1A）和5-HT（2A）受体基因表达的能力可能解释了性腺激素对情绪和抑郁症的影响。
