Salman Tabinda, Nawaz Shazia, Ikram Huma, Haleem Darakhshan Jabeen
Dr. Panjwani Center for Molecular Medicine and Drugs Research, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, Pakistan.
Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
Pak J Pharm Sci. 2019 May;32(3):899-903.
Methylphenidate (MPD), a psycho-stimulant is a prescription medicine for the treatment of Attention deficit hyperactivity disorder (ADHD). The drug is also being increasingly used by general population for enhancing cognition. Only few preclinical studies have been carried out on the effects of MPD on cognition and these studies show either an enhancement or impairment of memory following the administration of MPD. The present study was designed to evaluate the effects of different doses of methylphenidate on acquisition and retention of memory in Morris water-maze test. Twenty four male Albino Wistar rats (weighing 180-220gm) were randomly assigned to four groups: (1) Control (2) 0.5mg/kg (3) 2.5mg/kg (4) 5 mg/kg methylphenidate. Animals received drug or water orally before training phase. Memory acquisition was monitored 2hrs post drug administration while memory retention was determined next day. It was found that the clinically relevant doses of methylphenidate (0.5mg/kg and 2.5mg/kg) improved memory acquisition and its retention but higher dose (5mg/kg) impaired both. We suggest that MPD-induced increase of catecholamine neurotransmission may have a role in the improvement of water maze performance while agonist activity of the drug for 5HT-1A receptor in the impaired performance at high doses. Food intake and body weight changes were not affected by MPD administration due to short-term administration of the drug. Results may help in improving pharmaco-therapeutic use of MPD for ADHD.
哌甲酯（MPD）是一种精神振奋剂，是用于治疗注意力缺陷多动障碍（ADHD）的处方药。普通人群也越来越多地使用这种药物来提高认知能力。关于MPD对认知影响的临床前研究很少，这些研究表明，服用MPD后，记忆要么增强，要么受损。本研究旨在评估不同剂量的哌甲酯对Morris水迷宫试验中记忆获得和保持的影响。将24只雄性白化Wistar大鼠（体重180 - 220克）随机分为四组：（1）对照组（2）0.5毫克/千克（3）2.5毫克/千克（4）5毫克/千克哌甲酯。在训练阶段前，动物口服药物或水。给药后2小时监测记忆获得情况，第二天测定记忆保持情况。结果发现，临床上相关剂量的哌甲酯（0.5毫克/千克和2.5毫克/千克）改善了记忆获得和保持，但高剂量（5毫克/千克）则损害了两者。我们认为，MPD诱导的儿茶酚胺神经传递增加可能在改善水迷宫表现中起作用，而该药物对5HT - 1A受体的激动剂活性在高剂量时导致表现受损。由于药物的短期给药，食物摄入量和体重变化不受MPD给药的影响。研究结果可能有助于改善MPD用于ADHD的药物治疗。
