Cognition-enhancing effect of oral therapeutic doses of methylphenidate in rats

ABSTRACT

To determine the effects of oral therapeutic doses of methylphenidate, on memory. It was thought that long term use of methylphenidate possibly may lead to tolerance in the ability of the drug elicit enhancement of learning and memory. A dose-dependent effect may therefore help to extend the therapeutic use of the drug for better clinical response. Experimental / Analytic study. This study was conducted in the Department of Pharmacology, Faculty of pharmacy, University of Karachi, Karachi for a period of period of 4 weeks. Twenty-four male Albino Wister rats [weighing 180-220g] were randomly assigned to four groups, one control and 3 test groups. The experimental protocol was designed to administer methylphenidate orally two times daily for 4 weeks. Four groups were [i] Saline [1.0 ml/kg/ day], [ii] Methylphenidate [2mg/kg/day] [iii] Methylphenidate [5mg/kg/day] [iv] Methylphenidate [8mg/kg/day] treated groups. Behavioral activity of rats i.e. performance of rats in passive avoidance test was monitored weekly. The experiment was performed in a balanced design to avoid the order effect. In the present study methylphenidate treated rats exhibited an increased in Passive Avoidance learning as there was increased in the latency time to reach the punished compartment as compared to control rats. This memory improvement effect of methylphenidate on PA was dose dependent in 1[st] week as the rats treated with 8 mg/kg/day took greater time to reach the dark box than 5mg/kg/day and 2mg/kg/day, but in 2[nd], 3[rd] and 4[th] week it was seen that rats treated with fore mention doses took same time but greater than 1[st] week to enter the punishable compartment. It can be concluded that high dose produce greater cognitive effect in short term treatment than low and moderate doses, however in long-term treatment all the doses produce similar improvement in memory without tolerance in cognition