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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats
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Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

机译：有和没有亚急性氟西汀的饮食肌酸对大鼠的性别特异性抗抑郁作用

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The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies.
机译：代谢障碍在抑郁症的病理生理中的潜在作用促使研究人员评估肌酸的治疗功效，肌酸是一种在大脑和肌肉组织中发现的天然存在的能量和神经保护性化合物。越来越多的证据表明口服肌酸补充剂可减轻人和动物的抑郁症状。一个新的问题是，饮食中的肌酸与抗抑郁药物治疗相结合是否比单独使用任何一种化合物更有效。为了回答这个问题，进行了四项研究，以使用强制游泳试验在雄性和雌性大鼠中研究肌酸和小剂量氟西汀联合治疗的行为效果。将补充有0％，2％或4％w / w肌酸一水合物的粉状啮齿动物饲料喂养Sprague-Dawley大鼠5周。根据亚急性给药方案，给大鼠注射氟西汀（5.0或10.0 mg / kg）或盐水。与氟西汀治疗前未补充雌性大鼠相比，维持4％肌酸饮食的雌性大鼠表现出抗抑郁样作用。相反，肌酸不能可靠地改变男性的行为。在药物治疗和第二次强制游泳试验之后，肌酸的抗抑郁剂样特征仅在女性同时服用5.0 mg / kg氟西汀的情况下仍然很显着。而且，仅在女性中，与单独使用任一剂量的氟西汀相比，补充4％的肌酸都会产生更强的抗抑郁样行为特征。发情周期数据表明，卵巢激素影响肌酸的抗抑郁样作用。解决因治疗而引起的性别差异问题可能会影响我们对肌酸的了解，肌酸与抑郁行为的关系，并可能导致针对性别的治疗策略。

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