BACKGROUND Modafinil is approved for narcolepsy and achieved high success in off-label indications in memory-related disorders. However, chronic indiscriminate use of modafinil imposes several health hazards like hyperglycaemia, obesity and metabolic syndrome, owing to impairment of sleep-wake cycle, circadian-rhythm, and neurotransmission. The present protocol elucidates the effects of modafinil per se and diabetic complications apropos. METHODS Modafinil (100 and 200 mg/kg) was administered in rats from day 5-26. To induce type-2 diabetes, streptozotocin (STZ) was given on day 1, and blood glucose assessed on day 5. CPP (combination propranolol and phentolamine) was administered to antagonize sympathetic activity. After evaluation of cognitive functions, serum lipid profile, and biomarkers of oxidative stress and acetylcholinesterase (AChE) activity were assessed. RESULTS Subacute dosing of modafinil significantly elevated blood glucose levels, albeit considerably less than diabetic group, and attenuated brain oxidative stress and AChE activity. Modafinil caused significant dyslipidaemia, increased body weight, whereas modestly altered abdominal circumference (AC) and thoracic circumference (TC) in rats. Significant hyperglycaemia, derangement of serum lipid-profile, brain lipid peroxidation, cholinergic hypofunction, and decrease in body weight and ACTC was noted in diabetic rats. Modafinil (100 mg/kg) significantly potentiated the hyperglycaemia and dyslipidaemia, however, attenuated oxidative stress and AChE activity in diabetic rats. Modafinil increased short-term (working) memory but not long-term spatial memory in normal and diabetic rats. CPP infusion attenuated these effects of modafinil. CONCLUSION Subacute dosing of modafinil differentially modulates long-term and short-term memory subtypes, and also predisposes towards metabolic derangements.

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莫达非尼改善记忆功能会损害新陈代谢吗？解读莫达非尼在大鼠中的利弊的研究。

背景技术莫达非尼被批准用于发作性睡病，并在记忆相关疾病的标签外适应症中获得了很高的成功。然而，由于睡眠-唤醒周期，昼夜节律和神经传递的损害，长期不加选择地使用莫达非尼会造成多种健康危害，例如高血糖症，肥胖症和代谢综合征。本协议阐明了莫达非尼本身和糖尿病并发症的影响。方法从第5-26天开始以莫达非尼（100和200 mg / kg）对大鼠给药。为了诱导2型糖尿病，在第1天给予链脲佐菌素（STZ），并在第5天评估血糖。给予CPP（普萘洛尔和酚妥拉明联合用药）拮抗交感神经活性。在评估认知功能，血脂水平，评估氧化应激和乙酰胆碱酯酶（AChE）活性的生物标志物。结果莫达非尼的亚急性给药显着提高了血糖水平，尽管明显低于糖尿病组，并且减弱了脑氧化应激和AChE活性。莫达非尼引起明显的血脂异常，体重增加，而大鼠的腹围（AC）和胸围（TC）略有改变。在糖尿病大鼠中发现了明显的高血糖症，血清脂质分布紊乱，脑脂质过氧化，胆碱能功能减退，体重和ACTC降低。莫达非尼（100 mg / kg）显着增强了高血糖症和血脂异常，但是减弱了糖尿病大鼠的氧化应激和AChE活性。莫达非尼增加正常和糖尿病大鼠的短期（工作）记忆，但不增加长期空间记忆。CPP输注减弱了莫达非尼的这些作用。结论莫达非尼的亚急性剂量差异调节长期和短期记忆亚型，也容易引起代谢紊乱。