5-HT2A Receptor Activation Normalizes Exaggerated Fear Behavior in p-Chlorophenylalanine (PCPA)-Treated Rats.
5-HT2A Receptor Activation Normalizes Exaggerated Fear Behavior in p-Chlorophenylalanine (PCPA)-Treated Rats.
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DOI：
10.4236/jbbs.2012.24053
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发表时间：
2012-11-01
期刊：
影响因子：
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通讯作者：
Keele, N Bradley
中科院分区：
文献类型：
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作者：
Hughes, Cathryn R;Tran, Lee;Keele, N Bradley
血清素（5-羟色胺，5-HT）神经传递的缺陷与异常的情绪行为如攻击性、焦虑和抑郁有关。然而，涉及的具体5-HT受体机制还不清楚。用对氯苯丙氨酸（PCPA）降低大鼠脑内5-HT含量，观察5-HT_2受体在恐惧增强惊吓（FPS）中的作用。PCPA处理的大鼠显示出增强的FPS幅度。全身给予5-HT 2受体激动剂（±）-2，5-二甲氧基-4-碘苯丙胺盐酸盐（DOI）可降低PCPA处理和盐水（SAL）处理对照动物的FPS，使PCPA处理大鼠的过度恐惧反应正常化。在SAL和PCPA处理的动物中，DOI诱导的习得性恐惧减少被5-HT 2拮抗剂酮色林逆转，但不被5-HT 2B/2C拮抗剂SB 206553逆转。总之，这些发现表明5-HT 2A受体是习得性恐惧的关键调节因子，并且5-HT 2A受体可能是使由慢性5-HT能干扰引起的夸大的习得性恐惧正常化的重要药理学靶点。
Deficits in serotonin (5-hydroxytryptamine, 5-HT) neurotransmission are implicated in abnormal emotional behaviors such as aggression, anxiety, and depression. However, the specific 5-HT receptor mechanisms involved are not well understood. The role of 5-HT2 receptors in fear potentiated startle, (FPS) was examined in rats chronically treated with p-chlorophenylalanine (PCPA) to reduce brain 5-HT. PCPA-treated rats show an enhanced magnitude of FPS. Systemic administration of the 5-HT2 receptor agonist (±)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI) reduced FPS in both PCPA-treated and saline (SAL)-treated control animals, normalizing the exaggerated fear response in PCPA-treated rats. In both SAL- and PCPA-treated animals, the DOI-induced reduction of learned fear was reversed by the 5-HT2 antagonist ketanserin, but not by the 5-HT2B/2C antagonist SB 206553. Together, these findings suggest 5-HT2A receptors are critical regulators of learned fear, and that 5-HT2A receptors may be an important pharmacological target to normalize exaggerated learned fear resulting from chronic 5-HT-ergic disruption.