The Antidepressant Effect of L-Tyrosine-Loaded Nanoparticles: Behavioral Aspects
The Antidepressant Effect of L-Tyrosine-Loaded Nanoparticles: Behavioral Aspects
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DOI：
10.1159/000443575
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发表时间：
2016-07-01
影响因子：
1.5
通讯作者：
Abdelwahed, Wassim
中科院分区：
文献类型：
--
作者：
Alabsi, Abdelrahman;Khoudary, Adel Charbel;Abdelwahed, Wassim
背景：抑郁症与大脑中特定神经递质水平的破坏有关。 L-酪氨酸是一种以上受抑郁症影响的神经递质的前体。尽管单胺前体的缺点包括高剂量和低效率，但许多研究建议使用 L-酪氨酸作为抗抑郁药。目的：本研究的目的是通过大鼠急性和慢性轻度应激 (CMS) 抑郁模型的行为测试，探讨纳米颗粒设计配方中负载的 L-酪氨酸可能的抗抑郁作用。方法：两种模型的动物每天接受 L-酪氨酸负载纳米颗粒（5 或 10 mg/kg）、L-酪氨酸溶液（10 mg/kg）、氟西汀（10 mg/kg）或安慰剂，持续 21 天。来自抑郁症急性应激模型的大鼠接受旷场和强迫游泳测试（FST）。对于CMS模型，进行了蔗糖偏好测试。此外，还对纳米颗粒配方的 3 种情况进行了体外测试。体外试验获得了较高的溶出度和包封率。此外，负载 L-酪氨酸的纳米粒子 10 mg/kg 和氟西汀 10 mg/kg 显着减少了 FST 中的不动时间，同时恢复了运动活动、行走距离和站立计数的基础水平。此外，在用负载 L-酪氨酸的纳米粒子 10 mg/kg 和氟西汀 10 mg/kg 处理后，在蔗糖偏好测试中记录了蔗糖消耗的增加。结果：通过行为测试，用负载L-酪氨酸的纳米粒子治疗后的积极结果可能归因于恢复大脑去甲肾上腺素的基础水平。结论：L-酪氨酸给药对脑内酪氨酸羟化酶和促肾上腺皮质激素释放因子水平的影响值得进一步研究。 (C) 2016 S. Karger AG，巴塞尔
Background: Depression has been linked to disruption in the cerebral levels of specific neurotransmitters. L-tyrosine is a precursor of more than one of the neurotransmitters affected by depression. Even though setbacks of monoamines precursors include high doses and low efficiency, many studies have suggested using L-tyrosine as antidepressant. Purpose: The purpose of this study was to explore the possible antidepressant effect of L-tyrosine loaded in a nanoparticle-designed formula, using behavioral tests in acute and chronic mild stress (CMS) models of depression in rats. Methods: Animals from both models received L-tyrosine-loaded nanoparticles (5 or 10 mg/kg), L-tyrosine solution (10 mg/kg), fluoxetine (10 mg/kg) or placebo daily for 21 days. Rats from the acute stress model of depression were subjected to open field and forced swim tests (FSTs). For the CMS model, sucrose preference test was carried out. Additionally, 3 profiles of the nanoparticles formula were tested in vitro. High dissolution rate and entrapment efficiency were obtained from the in vitro tests. Moreover, L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg significantly decreased the immobility time in the FST, concomitant with restoration of the basal levels of locomotor activity, distance travelled and rearing counts. Also, an increase of the sucrose consumption was recorded in the sucrose preference test after treatment with L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg. Results: The positive results after treatment with L-tyrosine-loaded nanoparticles, through behavioral tests, are probably attributed to restorating the basal levels of the cerebral noradrenaline. Conclusion: The effects of L-tyrosine administration on the cerebral levels of tyrosine hydroxylase and corticotropin-releasing factor should be further investigated. (C) 2016 S. Karger AG, Basel