title: Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Neuroscience, Oberlin College, Science Center A241, 119 Woodland St., Oberlin, OH, 44074, USA, tpaine@oberlin.edu.
authors.forename: T A
authors.initials: TA
authors.lastname: Paine
authors.forename: A
authors.initials: A
authors.lastname: O'Hara
authors.forename: B
authors.initials: B
authors.lastname: Plaut
authors.forename: D C
authors.initials: DC
authors.lastname: Lowes
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003657:Decision Making / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists / Q000378:metabolism; D005715:Gambling / Q000378:metabolism* / Q000523:psychology*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline