Effects of chronic inhibition of GABA synthesis on attention and impulse control
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.
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.
Pharmacology Biochemistry and Behavior
Attention, Schizophrenia, GABA, Impulsive, GAD67, L-Allylglycine