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

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.

Publisher

Springer Verlag

Publication Date

11-26-2014

Publication Title

Psychopharmacology

Department

Neuroscience

Document Type

Article

DOI

https://dx.doi.org/10.1007/s00213-014-3816-7

Keywords

GABA(A) receptor, GAD67, Decision-making, Response inhibition, Medial prefrontal cortex, Schizophrenia, Bicuculline, L-Allylglycine

Language

English

Format

text

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