Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task

Title:
Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task
Authors:
Paine, Tracie A.
Abstract:
Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons. Thus it is hypothesized that reduced cortical GABA synthesis and release may contribute to the attention deficits in schizophrenia. Here the effect of reducing cortical GABA synthesis with L-allylglycine (LAG) on attention was tested using three different versions of the 5-choice serial reaction time task (5CSRTT). Because 5CSRTT performance can be affected by locomotor activity, we also measured this behavior in an open field. Finally, the expression of Fos protein was used as an indirect measure of reduced GABA synthesis. Intra-cortical LAG (10 μg/0.5 μl/side) infusions increased Fos expression and resulted in hyperactivity in the open field. Intra-cortical LAG infusions did not affect attention in any version of the 5CSRTT. These results suggest that a general decrease in GABA synthesis is not sufficient to cause attention deficits. It remains to be tested whether a selective decrease in GABA synthesis in parvalbumin-containing GABA neurons could cause attention deficits. Decreased cortical GABA synthesis did increase locomotor activity; this may reflect the positive symptoms of schizophrenia.
Citation:
Paine, Tracie. 2012. Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task. Neuropharmacology, Sep 26;65C:39-47. doi: 10.1016/j.neuropharm.2012.09.009
Publisher:
Elsevier
DATE ISSUED:
2012-09-26
Department:
Neuroscience
Type:
article
PUBLISHED VERSION:
10.1016/j.neuropharm.2012.09.009
PERMANENT LINK:
http://hdl.handle.net/11282/309662

Full metadata record

DC FieldValue Language
dc.contributor.authorPaine, Tracie A.en_US
dc.date.accessioned2013-12-23T16:14:31Zen
dc.date.available2013-12-23T16:14:31Zen
dc.date.issued2012-09-26en
dc.identifier.citationPaine, Tracie. 2012. Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task. Neuropharmacology, Sep 26;65C:39-47. doi: 10.1016/j.neuropharm.2012.09.009en_US
dc.identifier.issn0028-3908en_US
dc.identifier.urihttp://hdl.handle.net/11282/309662en
dc.description.abstractAttention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons. Thus it is hypothesized that reduced cortical GABA synthesis and release may contribute to the attention deficits in schizophrenia. Here the effect of reducing cortical GABA synthesis with L-allylglycine (LAG) on attention was tested using three different versions of the 5-choice serial reaction time task (5CSRTT). Because 5CSRTT performance can be affected by locomotor activity, we also measured this behavior in an open field. Finally, the expression of Fos protein was used as an indirect measure of reduced GABA synthesis. Intra-cortical LAG (10 μg/0.5 μl/side) infusions increased Fos expression and resulted in hyperactivity in the open field. Intra-cortical LAG infusions did not affect attention in any version of the 5CSRTT. These results suggest that a general decrease in GABA synthesis is not sufficient to cause attention deficits. It remains to be tested whether a selective decrease in GABA synthesis in parvalbumin-containing GABA neurons could cause attention deficits. Decreased cortical GABA synthesis did increase locomotor activity; this may reflect the positive symptoms of schizophrenia.en_US
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.identifier.doi10.1016/j.neuropharm.2012.09.009en
dc.subject.departmentNeuroscienceen_US
dc.titleInhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time tasken_US
dc.typearticleen_US
dc.identifier.journalNeuropharmacologyen_US
dc.subject.keywordAttentionen_US
dc.subject.keywordSchizophreniaen_US
dc.subject.keywordGABAen_US
dc.subject.keyword5-choice serial reaction time task (5CSRTT)en_US
dc.subject.keywordLocomotor activityen_US
dc.subject.keywordPrefontal cortexen_US
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