Memory improvement by modafinil at cost of metabolic hazards? A study to decipher the benefits and risks of modafinil in rats

Abstract

BackgroundModafinil 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. MethodsModafinil (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. ResultsSubacute 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. ConclusionSubacute dosing of modafinil differentially modulates long-term and short-term memory subtypes, and also predisposes towards metabolic derangements.