Hughes Cathryn R, Tran Lee, Keele N Bradley
Department of Psychology & Neuroscience, Baylor University, Waco, USA.
Institute of Biomedical Studies, Baylor University, Waco, USA.
J Behav Brain Sci. 2012 Nov;2(4):454-462. doi: 10.4236/jbbs.2012.24053.
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-HT receptors in fear potentiated startle, (FPS) was examined in rats chronically treated with -chlorophenylalanine (PCPA) to reduce brain 5-HT. PCPA-treated rats show an enhanced magnitude of FPS. Systemic administration of the 5-HT 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-HT antagonist ketanserin, but not by the 5-HT antagonist SB 206553. Together, these findings suggest 5-HT receptors are critical regulators of learned fear, and that 5-HT receptors may be an important pharmacological target to normalize exaggerated learned fear resulting from chronic 5-HT-ergic disruption.
血清素（5-羟色胺，5-HT）神经传递的缺陷与攻击、焦虑和抑郁等异常情绪行为有关。然而，所涉及的具体5-HT受体机制尚未得到充分理解。在长期用对氯苯丙氨酸（PCPA）处理以降低脑内5-HT的大鼠中，研究了5-HT受体在恐惧增强惊吓反应（FPS）中的作用。经PCPA处理的大鼠表现出增强的FPS幅度。5-HT受体激动剂盐酸（±）-2,5-二甲氧基-4-碘苯丙胺（DOI）的全身给药降低了PCPA处理组和生理盐水（SAL）处理的对照动物的FPS，使PCPA处理大鼠中过度的恐惧反应恢复正常。在SAL处理组和PCPA处理组动物中，DOI诱导的习得性恐惧降低均被5-HT拮抗剂酮色林逆转，但未被5-HT拮抗剂SB 206553逆转。这些发现共同表明，5-HT受体是习得性恐惧的关键调节因子，并且5-HT受体可能是使慢性5-HT能破坏导致的过度习得性恐惧恢复正常的重要药理学靶点。
