Clinically relevant doses of methylphenidate elicit behavioral sensitization and impair cognition on drug withdrawal in normal adult rats

Methylphenidate (MPD), a psychostimulant, is the first line drug for improving cognitive performance in attention deficit hyperactivity disorder (ADHD). A non-prescription use of this drug for improving performance is also becoming increasingly known. A growing rise in its medical and nonmedical use suggests that the drug is addictive.The present study was designed to ascertain the reinforcing and withdrawal effects of clinically relevant doses of methylphenidate on cognitive behavior of normal adult rats. Potential addictive effects and withdrawal effects on cognition were also determined.Effects of MPD in improving cognition were monitored after drug administration as well as withdrawal using Morris Water Maze test. Taking behavioral sensitization as an important contributing factor of drug addiction; addictive effects of MPD were also determined. Data analysis was done on SPSS version 13 by one-way and two-way ANOVA (repeated measure design) where applicable; post hoc comparisons were done by Tukey’s test. Repeated oral administration of MPD (0.5 and 1mg/kg) for six days produced behavioral sensitization and reduced daily food intake. After six days of treatment rats were repeatedly administered/withdrawal from repeated administration of MPD to investigate effects of MPD on cognitive behaviors. Results showed an improvement in cognition in rats repeatedly administered with MPD (0.5 and 1 mg/kg). Whereas, withdrawal from repeated administration of MPD impaired short term memory, long term memory and memory retention. Doses of MPD which improve learning and memory are potentially addictive and elicit behavioral sensitization. Use of drug in healthy subjects can impair performance below basal levels particularly in drug withdrawal conditions.