Early Adversity and Serotonin Transporter Genotype Interact With Hippocampal Glucocorticoid Receptor mRNA Expression, Corticosterone, and Behavior in Adult Male Rats
Early Adversity and Serotonin Transporter Genotype Interact With Hippocampal Glucocorticoid Receptor mRNA Expression, Corticosterone, and Behavior in Adult Male Rats
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DOI：
10.1037/a0022891
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发表时间：
2011-04-01
影响因子：
1.9
通讯作者：
Fleming, Alison S.
中科院分区：
文献类型：
--
作者：
Belay, Hiwote;Burton, Christie L.;Fleming, Alison S.
尽管其对发育很重要，但关于等位基因变异如何与产前和产后应激相互作用，我们所知相对较少。我们研究了血清素转运体（5 - HTT）基因型、产前和产后应激对成年雄性大鼠糖皮质激素受体（GR）mRNA表达、皮质类固醇应激反应以及行为的相互作用。产前应激包括从妊娠第10 - 21天每天对怀孕母鼠进行束缚。产后应激包括在分娩后由母鼠抚养幼崽（MR）或采用人工饲养（AR）模式，并伴有或不伴有额外的“类似舔舐”的抚摸刺激。对成年雄性大鼠后代测量了5 - HTT基因型、海马GR mRNA水平、皮质类固醇应激反应以及包括惊跳反应、前脉冲抑制（PPI）和运动活动在内的行为。我们发现，对于成年期海马GR mRNA水平和皮质酮应激反应，存在显著的基因型与产前应激相互作用。相比之下，行为终点往往更明显地受到基因型与产后环境之间相互作用的影响。这些研究结果表明，5 - HTT基因的等位基因变异与产前环境相互作用影响下丘脑 - 垂体 - 肾上腺（HPA）轴生理，与产后环境相互作用影响行为。这些结果首次表明5 - HTT基因的遗传变异在大鼠生理和行为中起作用。
Despite its importance for development, relatively little is known about how allelic variation interacts with both pre- and postnatal stress. We examined the interaction between serotonin transporter (5-HTT) genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroid stress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnant dams from gestational Day 10-21. Postnatal stress involved raising pups after parturition either by their mothers (MR) or in the artificial rearing (AR) paradigm, with or without additional "licking-like" stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, and behaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured in adult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampal GR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioral endpoints tended to be more clearly affected by an interaction between genotype and postnatal environment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatal environment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatal environment to affect behavior. These results are the first to indicate a role for genetic variation in the 5-HTT gene in physiology and behavior in the rat.