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

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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.

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Acknowledgments

The authors would like to thank Emily Denehy and Travis McCuddy for technical assistance.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychological Science, Northern Kentucky University, Highland Heights, KY, 41099, USA

    Justin R. Yates

  2. Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA

    Justin R. Yates, Michael T. Bardo & Joshua S. Beckmann

  3. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY, 40536, USA

    Seth R. Batten

  4. Center for Drug Abuse Research Translation, University of Kentucky, Lexington, KY, 40536, USA

    Michael T. Bardo

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  1. Justin R. Yates
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  2. Seth R. Batten
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  3. Michael T. Bardo
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  4. Joshua S. Beckmann
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Corresponding author

Correspondence to Joshua S. Beckmann.

Additional information

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

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Yates, J.R., Batten, S.R., Bardo, M.T. et al. Role of ionotropic glutamate receptors in delay and probability discounting in the rat. Psychopharmacology 232, 1187–1196 (2015). https://doi.org/10.1007/s00213-014-3747-3

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  • DOI: https://doi.org/10.1007/s00213-014-3747-3

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