Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTLPR)
Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTLPR)
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DOI：
10.1023/b:bege.0000017873.61607.be
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发表时间：
2004-05-01
影响因子：
2.6
通讯作者：
Cameron, JL
中科院分区：
文献类型：
--
作者：
Bethea, CL;Streicher, JM;Cameron, JL
焦虑是人类人格的一个正常方面，它可以表现为各种障碍和其他负面特质。焦虑症的主要治疗方法是一类被称为选择性5-羟色胺再吸收抑制剂（SSRI）的药物，它与5-羟色胺再吸收转运蛋白结合。编码该转运蛋白的基因的上游区域含有多态性，该多态性是插入/缺失事件，其进而在群体中产生长（l）和短（s）等位基因。5-羟色胺转运体中的这种特殊多态性，即5-羟色胺转运体连锁多态性区域（5-HTTLPR），被认为与焦虑特征和障碍的发生有关。大多数以人类为对象的研究都考察了成年人的行为，这些行为可能来自不同的经验和环境背景，以及遗传差异。为了更好地分离遗传学的影响，我们对128只婴儿和青少年猴子进行了5 HTTLPR基因分型，并在四种旨在引发恐惧焦虑行为的测试范式中测试了行为反应：自由玩耍，遥控汽车，人类入侵者和新水果测试。在自由玩耍测试中，s/s猴子被发现行为受到抑制，在遥控汽车测试中参与更多的恐惧行为，在人类入侵者测试的凝视部分中受到更多的威胁，尽管有少数猴子被评估。在催乳素对芬氟拉明的反应方面，基因型之间没有差异。这些数据表明，更大的焦虑，在s/s猴子的焦虑行为，这是独立的全球神经激素的挑战测试的不同方面。这些神经行为学数据支持了最近在人类中的神经影像学发现，表明5 HTTLPR对杏仁核依赖性焦虑行为的重要性。
Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and other negative traits. The primary treatment for anxiety is the class of drugs known as the selective serotonin reuptake inhibitors (SSRIs), which bind to the serotonin reuptake transporter. The upstream region of the gene that codes for this transporter contains a polymorphism that is an insertion/deletion event that in turn, produces long ( l) and short (s) alleles in the population. This particular polymorphism in the serotonin transporter, the 5HTTLPR ( serotonin transporter linked polymorphic region), is thought to be involved in the genesis of anxious traits and disorders. Most studies with human subjects have examined adult behavior, which may derive from diverse experiential and environmental backgrounds, as well as genetic differences. To better isolate the effect of genetics, we genotyped 128 infant and juvenile monkeys for the 5HTTLPR and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious behaviors: a free play, remote-controlled car, human intruder, and novel fruit test. The s/s monkeys were found to be behaviorally inhibited in the free play test, engaged in more fear behaviors in the remote-controlled car test, and threatened more in the stare portion of the human intruder test, even though a small number of monkeys were assessed. There was no difference between genotypes of either sex in the prolactin response to fenfluramine. These data indicate greater anxiety in the s/s monkeys for distinct facets of anxious behavior, which are independent of a global neurohormonal challenge test. These neurobehavioral data support recent neuroimaging findings in humans indicating the importance of the 5HTTLPR for amygdala-dependent anxious behavior.