Lee Bombi, Shim Insop, Lee Hyejung, Hahm Dae-Hyun
Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Center for Converging Humanities, College of Medicine, Kyung Hee University, Seoul 02447, Korea.
Korean J Physiol Pharmacol. 2018 Mar;22(2):183-192. doi: 10.4196/kjpp.2018.22.2.183. Epub 2018 Feb 23.
Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.
创伤后应激障碍（PTSD）是一种由创伤引起的精神障碍，其特征是恐惧消除受损、过度觉醒、焦虑、抑郁和失忆症状，这些症状可能涉及恐惧回路中单胺类物质的释放。本研究测量了几种与焦虑相关的行为反应，以检验小檗碱（BER）对单次长时间应激（SPS）暴露后大鼠焦虑症状的影响，并确定BER是否能逆转多巴胺（DA）功能障碍。SPS暴露后，大鼠连续14天接受BER（10、20或30mg/kg，腹腔注射，每日一次）。在高架十字迷宫试验中，给予BER显著增加了大鼠在开放臂的停留时间，减少了理毛行为；在旷场试验中，增加了大鼠在中央区域的停留时间和穿越中央区域的次数。BER恢复了神经化学异常以及SPS诱导的海马体和纹状体中DA组织水平的降低。BER治疗期间DA浓度的增加可能部分归因于海马体中酪氨酸羟化酶和DA转运体的mRNA表达，而BER对PTSD大鼠海马体中囊泡单胺转运体mRNA表达没有显著影响。这些结果表明，BER对与焦虑相关的行为和生化指标具有抗焦虑样作用。这些发现支持了降低焦虑在PTSD大鼠中改变多巴胺能传递并减轻焦虑的作用。因此，BER可能是一种治疗或缓解类似PTSD患者所观察到的精神障碍的有效药物。
