Cognition-Enhancing Effect of Oral Therapeutic Doses of Methylphenidate in Rats

Abstract

Objective: 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. 
Study Design: Experimental / Analytic study 
Place and Duration of 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. 
Materials and Methods: 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. 
Results: 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 1st 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 2nd, 3rd and 4th week it was seen that 
rats treated with fore mention doses took same time but greater than 1st week to enter the punishable compartment
Conclusion: 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