title: Role of ionotropic glutamate receptors in delay and probability discounting in the rat.
abstract: BACKGROUND
  Discounting of delayed and probabilistic reinforcement is linked to increased drug use and pathological gambling. Understanding the neurobiology of discounting is important for designing treatments for these disorders. Glutamate is considered to be involved in addiction-like behaviors; however, the role of ionotropic glutamate receptors (iGluRs) in discounting remains unclear.
  
  
  OBJECTIVE
  The current study examined the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor blockade on performance in delay and probability discounting tasks.
  
  
  METHODS
  Following training in either delay or probability discounting, rats (n = 12, each task) received pretreatments of the NMDA receptor antagonists MK-801 (0, 0.01, 0.03, 0.1, or 0.3 mg/kg, s.c.) or ketamine (0, 1.0, 5.0, or 10.0 mg/kg, i.p.), as well as the AMPA receptor antagonist CNQX (0, 1.0, 3.0, or 5.6 mg/kg, i.p.). Hyperbolic discounting functions were used to estimate sensitivity to delayed/probabilistic reinforcement and sensitivity to reinforcer amount.
  
  
  RESULTS
  An intermediate dose of MK-801 (0.03 mg/kg) decreased sensitivity to both delayed and probabilistic reinforcement. In contrast, ketamine did not affect the rate of discounting in either task but decreased sensitivity to reinforcer amount. CNQX did not alter sensitivity to reinforcer amount or delayed/probabilistic reinforcement.
  
  
  CONCLUSIONS
  These results show that blockade of NMDA receptors, but not AMPA receptors, decreases sensitivity to delayed/probabilistic reinforcement (MK-801) and sensitivity to reinforcer amount (ketamine). The differential effects of MK-801 and ketamine demonstrate that sensitivities to delayed/probabilistic reinforcement and reinforcer amount are pharmacologically dissociable.
authors.affiliation: Department of Psychological Science, Northern Kentucky University, Highland Heights, KY, 41099, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Yates
authors.forename: Seth R
authors.initials: SR
authors.lastname: Batten
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Beckmann
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D065786:Delay Discounting / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012054:Reinforcement, Psychology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058468:Receptors, Ionotropic Glutamate