Department of Psychology, SUNY Old Westbury, Old Westbury, NY, USA.
SUNY Neuroscience Research Institute, SUNY Old Westbury, Old Westbury, NY, USA.
Adv Exp Med Biol. 2019;1155:801-819. doi: 10.1007/978-981-13-8023-5_69.
Lead (Pb) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb-exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb-exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb-exposure with no gender differences observed. However, Pb-exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.
铅（Pb）是一种发育神经毒物，会导致大脑兴奋-抑制（E/I）平衡的改变。牛磺酸通过 GABA-AR 增加氯离子浓度，作为一种有效的抑制性化合物，有助于维持大脑兴奋性的适当水平。考虑到牛磺酸通过 GABA-AR 促进抑制的这种药理学机制，本初步研究旨在探索牛磺酸衍生物的抗焦虑潜力。实验组包括以下发育性 Pb 暴露组：对照组（0ppm）和围产期（饮用水中 150ppm 或 1000ppm 醋酸铅）。大鼠在出生后第 36-45 天进行行为测试，随机分配到盐水、牛磺酸或牛磺酸衍生化合物（即 TD-101、TD-102 或 TD-103）溶液中，以评估大鼠对每种药物的反应能力，通过 GABA 能系统减轻发育性 Pb 暴露的影响。长耳罩大鼠通过旷场（OF）测试进行初步运动评估。OF 后约 24 小时，相同的大鼠被暴露于高架十字迷宫（EPM）中，并在测试前 15 分钟给予 43mg/kg 的盐水、牛磺酸或 TD 药物的腹腔注射。每个大鼠根据药理学条件使用随机分配方法进行测试，测试采用三重盲法进行。OF 数据显示，运动活性不受 Pb 暴露的影响，也没有观察到性别差异。然而，Pb 暴露在 EPM 中引起了焦虑反应，有趣的是，牛磺酸和 TD 药物以性别特异性的方式改善了这种焦虑反应。雌性大鼠比雄性大鼠表现出更多的焦虑行为；因此，表现出更大程度的焦虑，而牛磺酸及其衍生物作为药物治疗可以恢复这种焦虑。本精神药理学初步研究的结果表明，牛磺酸及其衍生物可能为进一步探索牛磺酸的药理学机制和作用以及相关的 GABA 受体特性提供有用的数据，这些化合物通过减轻焦虑作为治疗焦虑和其他相关情绪障碍的潜在行为药理学治疗方法。
