A comparison of methylphenidate enantiomers on delay discounting in rats

Abstract

Three forms of methylphenidate (MPH) are currently used in treating attention‐deficit hyperactivity disorder (ADHD): Ritalin (dl‐MPH), Focalin (d‐MPH), and Daytrana (dl‐MPH), a transdermal system producing higher levels of l‐MPH than dl‐ MPH as it avoids the first‐pass metabolism of oral administration. The current study compared MPH enantiomers using a delay‐discounting procedure in rats which is thought to assess “impulsivity” (a key characteristic of ADHD). Sprague‐Dawley rats (n=5) were trained to emit either of two responses, one producing an immediate 45‐g food pellet, the other producing four such pellets delivered at increasing delays (0, 8, 32 s). The percent selection of the larger food amount was graphed as a function of delay with the area under the curve (AUC) assessed. Increases in AUC are consistent with decreases in “impulsivity” (i.e., selection of the smaller, immediate over the larger, delayed reinforcer). Systemic (i.p.) administration of dl‐MPH and d‐MPH dose‐dependently increased AUC, while l‐MPH, morphine and pentobarbital did not change the AUC. The present results indicate that delay discounting can be used to identify treatments for ADHD, and that d‐MPH, but not l‐MPH, is active in this procedure, which is in agreement with the current understanding of the therapeutic actions of MPH.