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

Title:
Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task
Authors:
Paine, Tracie A.; O’Hara, A.; Plaut, B.; Lowes, Daniel C.
Abstract:
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. The goal of this experiment was to determine whether disrupting cortical GABA transmission impairs decision-making using a rodent gambling task (rGT). 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 GABA(A) receptor antagonist bicuculline methiodide (BMI) or the GABA synthesis inhibitor l-allylglycine (LAG) on performance on the rGT were assessed. Intracortical infusions of BMI (25 ng/mu l/side), but not LAG (10 mu g/mu l/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. Blocking GABA(A) 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.
Citation:
Paine, T.A., A. O'Hara, B. Plaut, and D.C. Lowes. 2015. "Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task." Psychopharmacology 232(10): 1755-1765.
Publisher:
Springer Verlag
DATE ISSUED:
2014-11-26
Department:
Neuroscience
Type:
Article
PUBLISHED VERSION:
10.1007/s00213-014-3816-7
Additional Links:
http://link.springer.com/10.1007/s00213-014-3816-7
PERMANENT LINK:
http://hdl.handle.net/11282/594410

Full metadata record

DC FieldValue Language
dc.contributor.authorPaine, Tracie A.en
dc.contributor.authorO’Hara, A.en
dc.contributor.authorPlaut, B.en
dc.contributor.authorLowes, Daniel C.en
dc.date.accessioned2016-01-20T14:47:24Zen
dc.date.available2016-01-20T14:47:24Zen
dc.date.issued2014-11-26en
dc.identifier.citationPaine, T.A., A. O'Hara, B. Plaut, and D.C. Lowes. 2015. "Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task." Psychopharmacology 232(10): 1755-1765.en
dc.identifier.issn0033-3158en
dc.identifier.urihttp://hdl.handle.net/11282/594410en
dc.description.abstractDecision-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. The goal of this experiment was to determine whether disrupting cortical GABA transmission impairs decision-making using a rodent gambling task (rGT). 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 GABA(A) receptor antagonist bicuculline methiodide (BMI) or the GABA synthesis inhibitor l-allylglycine (LAG) on performance on the rGT were assessed. Intracortical infusions of BMI (25 ng/mu l/side), but not LAG (10 mu g/mu l/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. Blocking GABA(A) 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.en
dc.language.isoen_USen
dc.publisherSpringer Verlagen
dc.identifier.doi10.1007/s00213-014-3816-7en
dc.relation.urlhttp://link.springer.com/10.1007/s00213-014-3816-7en
dc.subject.departmentNeuroscienceen_US
dc.titleEffects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling tasken_US
dc.typeArticleen
dc.identifier.journalPsychopharmacologyen
dc.subject.keywordGABA(A) receptoren_US
dc.subject.keywordGAD67en_US
dc.subject.keywordDecision-makingen_US
dc.subject.keywordResponse inhibitionen_US
dc.subject.keywordMedial prefrontal cortexen_US
dc.subject.keywordSchizophreniaen_US
dc.subject.keywordBicucullineen_US
dc.subject.keywordL-Allylglycineen_US
dc.identifier.volume232en_US
dc.identifier.issue10en_US
dc.identifier.startpage1755en_US
dc.rightsArchived with thanks to Psychopharmacologyen
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