Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks.
Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks.
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DOI：
10.1111/j.1601-183x.2010.00652.x
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Gingrich JA
中科院分区：
文献类型：
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作者：
Muller JM;Morelli E;Ansorge M;Gingrich JA
血清素转运蛋白 (5-HTT) 功能的调节会导致人类和啮齿动物的情感行为发生变化。生活压力事件同样会影响情绪行为。在人类中，低表达的 5-htt 基因变体（5-htt 启动子区域的 s 等位基因）仅在有压力生活事件史的情况下与抑郁症风险增加相关。为了通过小鼠环境相互作用研究该基因，我们比较了不可避免的电击对野生型（5-htt+/+）、杂合子（5-htt+/-）和血清素转运蛋白缺陷（5-htt−/−）小鼠行为的影响。不可避免的电击会引起行为变化，包括在随后的测试中当可能逃脱时出现电击逃避缺陷。通过环境相互作用确认基因，我们发现压力以基因剂量依赖性方式增加逃避潜伏期（5-htt−/− > 5-htt+/- > 5-htt +/+），而在无压力条件下，基因型之间没有差异。逃避潜伏期增加的脆弱性不能通过增强的恐惧学习来解释，因为 5-htt−/− 小鼠没有表现出增强的恐惧条件反射。 5-htt 基因型和压力的相互作用似乎产生了选择性行为脆弱性，因为在其他焦虑和抑郁相关行为的测量中没有观察到 5-htt 基因型和压力的相互作用，包括开放场地、新奇抑制进食和强迫游泳测试。我们重复了之前的发现，即 5-htt−/− 在基线（无压力条件）下表现出高度的焦虑和抑郁样行为。总之，我们的数据为未来通过此处演示的应激相互作用研究 5-htt 基因型的神经基础提供了可能性。
Modulation of serotonin transporter (5-HTT) function causes changes in affective behavior, both in humans and rodents. Stressful life events likewise affect emotional behavior. In humans, a low-expressing genetic 5-htt variant, the s allele of the 5-htt linked promoter region, has been associated with increased risk for depression only where there was a history of stressful life events. To investigate this gene by environment interaction in mice, we compared the effects of inescapable shocks on the behavior of wild-type (5-htt+/+), heterozygote (5-htt+/−), and serotonin transporter deficient (5-htt−/−) mice. Inescapable shocks induce behavioral changes including a shock escape deficit, in a subsequent test when escape is possible. Confirming a gene by environment interaction, we found that stress increases escape latencies in a gene-dose dependent manner (5-htt−/− > 5-htt+/− > 5-htt +/+), where as there were no differences among the genotypes in the unstressed condition. The vulnerability to increased escape latency could not be accounted for by enhanced fear learning, as 5-htt−/− mice did not show heightened fear conditioning. The interaction of 5-htt genotype and stress appeared to produce a selective behavioral vulnerability, because no interaction of 5-htt genotype and stress was observed in other measures of anxiety and depression-linked behavior, including the open field, novelty suppressed feeding, and forced swim tests. We replicated prior findings that the 5-htt−/− displays heightened anxiety and depression-like behavior at baseline (unstressed condition). In conclusion, our data offers the possibility for future investigation of the neural basis underlying 5-htt genotype by stress interaction demonstrated here.