Effects of chronic inhibition of GABA synthesis on attention and impulse control

Title:
Effects of chronic inhibition of GABA synthesis on attention and impulse control
Authors:
Paine, Tracie A.; Cooke, Elizabeth K.; Lowes, Daniel C.
Abstract:
Background: Cortical GABA regulates a number of cognitive functions including attention and working memory and is dysregulated in a number of psychiatric conditions. In schizophrenia for example, changes in GABA neurons [reduced expression of glutamic acid decarboxylase (GAD), parvalbumin (PV) and the GABA reuptake transporter (GAT1)] suggest reduced cortical GABA synthesis and release; these changes are hypothesized to cause the cognitive deficits observed in this disorder. The goals of this experiment were to determine whether chronically reducing GAD function within the rat PFC causes attention deficits and alterations in PV and GAT1 expression. Methods: Male Sprague Dawley rats were trained on the 5-choice serial reaction time task (5CSRTT, a task of attention) until they reached criterion performance and then were implanted with a bilateral cannula aimed at the medial PFC. Cannulae were connected to osmotic minipumps that infused the GAD inhibitor L-allylglycine (LAG, 3.2 mu g/0.5 mu l/h) for 13 days. Following a 5-day recovery from surgery rats were tested on the standard 5CSKIT for 5 consecutive days and then tested on two modifications of the 5CSRTT. Finally, locomotor activity was assessed and the rats sacrificed. Brains were rapidly extracted and flash frozen and analyzed for the expression of GAD67, PV, GAT1 and the obligatory NMDA receptor subunit NR1. Results: Chronic LAG infusions transiently impaired attention, persistently impaired impulse control and increased locomotor activity. Behavioral changes were associated with an upregulaton of GAD67, but no change in PV, GAT1 or NR1 expression. Summary: Chronic inhibition of GABA synthesis within the medial PFC, increased impulsive behavior and locomotion, but did not impair attention; results consistent with previous research following acute inhibition of GABA synthesis. Moreover, our data do not support the hypothesis that decreasing GABA synthesis and release is sufficient to cause changes in other GABA-related proteins. (C) 2015 Elsevier Inc. All rights reserved.
Citation:
Paine, Tracie A., Elizabeth K. Cooke, and Daniel C. Lowes. 2015. "Effects of chronic inhibition of GABA synthesis on attention and impulse control." Pharmacology Biochemistry and Behavior 135: 97-104.
Publisher:
Elsevier
DATE ISSUED:
2015-08
Department:
Neuroscience
Type:
Article
PUBLISHED VERSION:
10.1016/j.pbb.2015.05.019
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0091305715300083
PERMANENT LINK:
http://hdl.handle.net/11282/594052

Full metadata record

DC FieldValue Language
dc.contributor.authorPaine, Tracie A.en
dc.contributor.authorCooke, Elizabeth K.en
dc.contributor.authorLowes, Daniel C.en
dc.date.accessioned2016-01-19T14:38:37Zen
dc.date.available2016-01-19T14:38:37Zen
dc.date.issued2015-08en
dc.identifier.citationPaine, Tracie A., Elizabeth K. Cooke, and Daniel C. Lowes. 2015. "Effects of chronic inhibition of GABA synthesis on attention and impulse control." Pharmacology Biochemistry and Behavior 135: 97-104.en
dc.identifier.issn0091-3057en
dc.identifier.urihttp://hdl.handle.net/11282/594052en
dc.description.abstractBackground: Cortical GABA regulates a number of cognitive functions including attention and working memory and is dysregulated in a number of psychiatric conditions. In schizophrenia for example, changes in GABA neurons [reduced expression of glutamic acid decarboxylase (GAD), parvalbumin (PV) and the GABA reuptake transporter (GAT1)] suggest reduced cortical GABA synthesis and release; these changes are hypothesized to cause the cognitive deficits observed in this disorder. The goals of this experiment were to determine whether chronically reducing GAD function within the rat PFC causes attention deficits and alterations in PV and GAT1 expression. Methods: Male Sprague Dawley rats were trained on the 5-choice serial reaction time task (5CSRTT, a task of attention) until they reached criterion performance and then were implanted with a bilateral cannula aimed at the medial PFC. Cannulae were connected to osmotic minipumps that infused the GAD inhibitor L-allylglycine (LAG, 3.2 mu g/0.5 mu l/h) for 13 days. Following a 5-day recovery from surgery rats were tested on the standard 5CSKIT for 5 consecutive days and then tested on two modifications of the 5CSRTT. Finally, locomotor activity was assessed and the rats sacrificed. Brains were rapidly extracted and flash frozen and analyzed for the expression of GAD67, PV, GAT1 and the obligatory NMDA receptor subunit NR1. Results: Chronic LAG infusions transiently impaired attention, persistently impaired impulse control and increased locomotor activity. Behavioral changes were associated with an upregulaton of GAD67, but no change in PV, GAT1 or NR1 expression. Summary: Chronic inhibition of GABA synthesis within the medial PFC, increased impulsive behavior and locomotion, but did not impair attention; results consistent with previous research following acute inhibition of GABA synthesis. Moreover, our data do not support the hypothesis that decreasing GABA synthesis and release is sufficient to cause changes in other GABA-related proteins. (C) 2015 Elsevier Inc. All rights reserved.en
dc.language.isoen_USen
dc.publisherElsevieren
dc.identifier.doi10.1016/j.pbb.2015.05.019en
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0091305715300083en
dc.subject.departmentNeuroscienceen_US
dc.titleEffects of chronic inhibition of GABA synthesis on attention and impulse controlen_US
dc.typeArticleen
dc.identifier.journalPharmacology Biochemistry and Behavioren
dc.subject.keywordAttentionen_US
dc.subject.keywordSchizophreniaen_US
dc.subject.keywordGABAen_US
dc.subject.keywordImpulsiveen_US
dc.subject.keywordGAD67en_US
dc.subject.keywordL-Allylglycineen_US
dc.identifier.volume135en_US
dc.identifier.startpage97en_US
dc.rightsArchived with thanks to Pharmacology Biochemistry and Behavioren
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