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.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Paine TA,O'Hara A,Plaut B,Lowes DCdoi
10.1007/s00213-014-3816-7subject
Has Abstractpub_date
2015-05-01 00:00:00pages
1755-65issue
10eissn
0033-3158issn
1432-2072journal_volume
232pub_type
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