title: Methylphenidate and impulsivity: a comparison of effects of methylphenidate enantiomers on delay discounting in rats.
abstract: BACKGROUND
  Current formulations of methylphenidate (MPH) used in treatment of attention-deficit/hyperactivity disorder (ADHD) result in significantly different bioavailability of MPH enantiomers. Daytrana®, a dl-MPH transdermal patch system, produces higher levels of l-MPH than when dl-MPH is administered orally (e.g., Ritalin®). One potential limitation of increased l-MPH was indicated in a preclinical study showing l-MPH may attenuate effects of d-MPH.
  
  
  OBJECTIVE
  The objective of the study was to investigate the interactive effects of MPH enantiomers by (1) assessing drug effects via a preclinical model of "impulsivity" and (2) performing a quantitative dose equivalence analysis of MPH enantiomer interactions.
  
  
  METHODS
  Sprague-Dawley rats were trained to emit either of two responses, one producing an immediate food pellet, the other producing four pellets delivered at increasing delays (0, 8, and 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).
  
  
  RESULTS
  Systemic administration of dl-MPH and d-MPH dose-dependently increased AUC, while l-MPH, morphine, and pentobarbital did not alter AUC. An analysis based upon dose equivalence indicated that dl-MPH produced additive effects that were not different from that predicted from effects of the enantiomers administered alone.
  
  
  CONCLUSIONS
  The present results indicate pharmacologically selective effects in that only drugs prescribed for the treatment of ADHD symptoms decreased a measure of "impulsivity" and that l-MPH likely does not attenuate or enhance the effects of d-MPH in the current delay-discounting task.
authors: Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Suite 200, Baltimore, MD, 21224, USA.
authors: Jonathan M
authors: JM
authors: Slezak
authors: George A
authors: GA
authors: Ricaurte
authors: Ronald J
authors: RJ
authors: Tallarida
authors: Jonathan L
authors: JL
authors: Katz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000523:psychology*; D008297:Male; D008774:Methylphenidate / Q000737:chemistry / Q000494:pharmacology*; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
references: Drugs. 2006;66(8):1117-26
references: 16789796
references: Psychopharmacology (Berl). 2004 Apr;173(1-2):167-74
references: 14752586
references: Biol Psychiatry. 2006 Jul 1;60(1):66-73
references: 16125144
references: J Exp Anal Behav. 2007 May;87(3):337-47
references: 17575900
references: Int J Neuropsychopharmacol. 2012 Nov;15(10):1473-87
references: 22094071
references: Psychopharmacology (Berl). 2002 Feb;160(1):92-8
references: 11862378
references: J Exp Anal Behav. 2005 May;83(3):297-314
references: 16047609
references: CNS Drugs. 2006;20(9):713-38
references: 16953648
references: Behav Pharmacol. 2009 Sep;20(5-6):424-36
references: 19730365
references: Pharmacotherapy. 2009 Jun;29(6):656-79
references: 19476419
references: Psychopharmacology (Berl). 2007 Aug;193(2):215-23
references: 17406857
references: J Exp Anal Behav. 2008 Jan;89(1):71-91
references: 18338676
references: J Exp Anal Behav. 2013 Jan;99(1):3-13
references: 23344985
references: Psychopharmacology (Berl). 1996 Nov;128(2):161-70
references: 8956377
references: Psychopharmacology (Berl). 2000 Nov;152(4):362-75
references: 11140328
references: J Clin Psychopharmacol. 2008 Jun;28(3 Suppl 2):S54-61
references: 18480678
references: Pharmacol Biochem Behav. 2011 Oct;99(4):545-51
references: 21669219
references: Pharmacol Ther. 2010 Aug;127(2):165-74
references: 20546783
references: Brain Res. 2011 Jun 17;1396:45-53
references: 21570676
references: Pharmacol Biochem Behav. 2008 Aug;90(2):184-97
references: 18456311
references: J Exp Anal Behav. 2001 Sep;76(2):235-43
references: 11599641
references: Nature. 1976 Nov 4;264(5581):57-9
references: 12471
references: Pharmacol Biochem Behav. 2012 May;101(3):403-16
references: 22342664
references: Behav Processes. 2009 Jun;81(2):264-9
references: 19429220
references: J Neurochem. 1997 May;68(5):2032-7
references: 9109529
references: J Exp Psychol Anim Behav Process. 1983 Apr;9(2):171-201
references: 6842136
references: J Pharmacol Exp Ther. 1987 Apr;241(1):300-6
references: 3572792
references: Pediatrics. 1983 Jul;72(1):56-9
references: 6866592
references: Exp Clin Psychopharmacol. 2009 Oct;17(5):291-301
references: 19803628
references: J Pharmacol Exp Ther. 1987 Apr;241(1):152-8
references: 3572779