Role of ionotropic glutamate receptors in delay and probability discounting in the rat

Justin R. Yates, Seth R. Batten, Michael T. Bardo, Joshua S. Beckmann

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Rationale: 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. Objectives: 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.

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalPsychopharmacology
Volume232
Issue number7
DOIs
StatePublished - Apr 2015

Bibliographical note

Funding Information:
The current study was supported by NIH grants P50 DA05312, R01 DA12964, K99 DA033373, and T32 DA016176.

Publisher Copyright:
© 2014 Springer-Verlag Berlin Heidelberg.

Keywords

  • AMPA receptor
  • Delayed reinforcement
  • Discounting
  • NMDA receptor
  • Probabilistic reinforcement
  • Rat

ASJC Scopus subject areas

  • Pharmacology

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