title: Effects of N-methyl-D-aspartate receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure.
abstract: The N-methyl-D-aspartate (NMDA) receptor has been recently identified as an important mediator of impulsive choice, as assessed in delay discounting. Although discounting is independently influenced by sensitivity to reinforcer magnitude and delayed reinforcement, few studies have examined how NMDA receptor ligands differentially affect these parameters.
  
  
  
  The current study examined the effects of various NMDA receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure.
  
  
  
  Following behavioral training, rats received treatments of the following NMDA receptor ligands: the uncompetitive antagonists ketamine (0, 1.0, 5.0, or 10.0 mg/kg; i.p.), MK-801 (0, 0.003, 0.01, or 0.03 mg/kg; s.c.), and memantine (0, 2.5, 5.0, or 10.0 mg/kg; i.p.), the competitive antagonist CGS 19755 (0, 5.0, 10.0, or 20.0 mg/kg; s.c.), the non-competitive NR2B subunit-selective antagonist ifenprodil (0, 1.0, 3.0, or 10.0 mg/kg; i.p), and the partial agonist D-cycloserine (0, 3.25, 15.0, or 30.0 mg/kg; s.c.).
  
  
  
  When an exponential model was used to describe discounting, CGS 19755 (5.0 mg/kg) increased impulsive choice without altering sensitivity to reinforcer magnitude. Conversely, ketamine (10.0 mg/kg), memantine (5.0 mg/kg), and ifenprodil (10.0 mg/kg) decreased sensitivity to reinforcer magnitude without altering impulsive choice. MK-801 and D-cycloserine did not alter delay-discounting performance, although two-way ANOVA analyses indicated D-cycloserine (15.0 mg/kg) decreased impulsive choice.
  
  
  
  The behavioral changes observed in delay discounting following administration of NMDA receptor antagonists do not always reflect an alteration in impulsive choice. These results emphasize the utility in employing quantitative methods to assess drug effects in delay discounting.
authors.affiliation: Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA. yatesj1@nku.edu.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Gunkel
authors.affiliation: Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Rogers
authors.affiliation: Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.
authors.forename: Mallory N
authors.initials: MN
authors.lastname: Hughes
authors.affiliation: Department of Psychological Science, Northern Kentucky University, 1 Nunn Drive, Highland Heights, KY, 41099, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Prior
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects; D003523:Cycloserine / Q000494:pharmacology; D065786:Delay Discounting / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007175:Impulsive Behavior / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008559:Memantine / Q000494:pharmacology; D010875:Pipecolic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012054:Reinforcement, Psychology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D010875:Pipecolic Acids; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D007649:Ketamine; D016291:Dizocilpine Maleate; D003523:Cycloserine; C010739:ifenprodil; D008559:Memantine
keywords: Delay discounting; Impulsive choice; NMDA receptor; Rat; Sensitivity to delayed reinforcement; Sensitivity to reinforcer magnitude