Abstract：
BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated.
METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance.
RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine.
CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.
METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance.
RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine.
CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.
摘要：
背景：黄酮类化合物chrysin在大鼠体内产生快速而持久的抗焦虑和抗抑郁作用。然而,尚不清楚低剂量和高剂量的chrysin是否通过γ-氨基丁酸亚型A（GABAA）受体产生不同的抗固定作用。因此，这项工作的目的是在纵向研究中比较低剂量和高剂量的chrysin对抑郁样行为的影响。此外，将chrysin与5-羟色胺能的氟西汀和γ-氨基丁酸（GABA）能的别孕烯醇酮进行了比较，并且还研究了其在慢性治疗后与GABAA受体的关系。
方法：雄性Wistar大鼠分为五组（每组n=8）：载体，1mg/kg的chrysin，5mg/kg的chrysin，1毫克/千克氟西汀，和1mg/kg别孕烷醇酮。在第一个实验中,每天注射治疗，并在治疗的0、1、14和28天评估对运动活动和强迫游泳测试的影响，和最终治疗后48小时。在第二个实验中,相似组接受注射1mg/kg黄质毒素治疗28天,以研究GABAA受体的作用.根据实验设计，使用单向和双向方差分析(ANOVA)检验进行统计分析，以p<0.05为显著性标准。
结果：在两个实验中，治疗没有改变运动活动.然而,低剂量和高剂量的chrysin,别孕烯醇酮,在强迫游泳试验中，氟西汀逐渐产生抗抑郁样作用，并在治疗后48小时内保持这种效果，除了低剂量的chrysin.piclotoxin阻断了低剂量chrysin产生的抗抑郁作用，但不影响高剂量的chrysin产生的那些，别孕烯醇酮,或者氟西汀.
结论：由低剂量和高剂量的chrysin引起的不同的抗抑郁样作用是时间依赖性的。低剂量的chrysin产生快速的抗抑郁作用，而高剂量的chrysin产生延迟但持续的效果，甚至在戒断后48小时。高剂量的chrysin的作用与别孕烯醇酮和氟西汀的作用相似。低chrysin类抗抑郁作用的机制似乎是GABA能，而高剂量的chrysin的作用可能涉及与5-羟色胺能系统相关的其他神经传递和神经调节系统。
方法：雄性Wistar大鼠分为五组（每组n=8）：载体，1mg/kg的chrysin，5mg/kg的chrysin，1毫克/千克氟西汀，和1mg/kg别孕烷醇酮。在第一个实验中,每天注射治疗，并在治疗的0、1、14和28天评估对运动活动和强迫游泳测试的影响，和最终治疗后48小时。在第二个实验中,相似组接受注射1mg/kg黄质毒素治疗28天,以研究GABAA受体的作用.根据实验设计，使用单向和双向方差分析(ANOVA)检验进行统计分析，以p<0.05为显著性标准。
结果：在两个实验中，治疗没有改变运动活动.然而,低剂量和高剂量的chrysin,别孕烯醇酮,在强迫游泳试验中，氟西汀逐渐产生抗抑郁样作用，并在治疗后48小时内保持这种效果，除了低剂量的chrysin.piclotoxin阻断了低剂量chrysin产生的抗抑郁作用，但不影响高剂量的chrysin产生的那些，别孕烯醇酮,或者氟西汀.
结论：由低剂量和高剂量的chrysin引起的不同的抗抑郁样作用是时间依赖性的。低剂量的chrysin产生快速的抗抑郁作用，而高剂量的chrysin产生延迟但持续的效果，甚至在戒断后48小时。高剂量的chrysin的作用与别孕烯醇酮和氟西汀的作用相似。低chrysin类抗抑郁作用的机制似乎是GABA能，而高剂量的chrysin的作用可能涉及与5-羟色胺能系统相关的其他神经传递和神经调节系统。
