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Psychopharmacology

, Volume 232, Issue 10, pp 1755–1765 | Cite as

Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task

  • T. A. PaineEmail author
  • A. O’Hara
  • B. Plaut
  • D. C. Lowes
Original Investigation

Abstract

Rationale

Decision-making is a complex cognitive process that is mediated, in part, by subregions of the medial prefrontal cortex (PFC). Decision-making is impaired in a number of psychiatric conditions including schizophrenia. Notably, people with schizophrenia exhibit reductions in GABA function in the same PFC areas that are implicated in decision-making. For example, expression of the GABA-synthesizing enzyme GAD67 is reduced in the dorsolateral PFC of people with schizophrenia.

Objectives

The goal of this experiment was to determine whether disrupting cortical GABA transmission impairs decision-making using a rodent gambling task (rGT).

Methods

Rats were trained on the rGT until they reached stable performance and then were implanted with guide cannulae aimed at the medial PFC. Following recovery, the effects of intra-PFC infusions of the GABAA receptor antagonist bicuculline methiodide (BMI) or the GABA synthesis inhibitor l-allylglycine (LAG) on performance on the rGT were assessed.

Results

Intracortical infusions of BMI (25 ng/μl/side), but not LAG (10 μg/μl/side), altered decision-making. Following BMI infusions, rats made fewer advantageous choices. Follow-up experiments suggested that the change in decision-making was due to a change in the sensitivity to the punishments, rather than a change in the sensitivity to reward magnitudes, associated with each outcome. LAG infusions increased premature responding, a measure of response inhibition, but did not affect decision-making.

Conclusions

Blocking GABAA receptors, but not inhibiting cortical GABA synthesis, within the medial PFC affects decision-making in the rGT. These data provide proof-of-concept evidence that disruptions in GABA transmission can contribute to the decision-making deficits in schizophrenia.

Keywords

GABAA receptor GAD67 Decision-making Response inhibition Medial prefrontal cortex Schizophrenia Rat Bicuculline l-Allylglycine 

Notes

Acknowledgments

This work was supported by NIH grant R15MH098246 awarded to TAP.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • T. A. Paine
    • 1
    Email author
  • A. O’Hara
    • 1
  • B. Plaut
    • 1
  • D. C. Lowes
    • 1
  1. 1.Department of NeuroscienceOberlin CollegeOberlinUSA

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