The influence of NMDA and GABA(A) receptors and glutamic acid decarboxylase (GAD) activity on attention

NMDA 和 GABA(A) 受体及谷氨酸脱羧酶 (GAD) 活性对注意力的影响

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作者:Alan L Pehrson, Corina O Bondi, Nelson K B Totah, Bita Moghaddam

Conclusions

These data demonstrate that, while tonic stimulation of NMDA and GABA(A) receptors within the ACC are critical for attentional performance, reduction in GAD activity may have little functional significance and is not indicative of reduced GABA neurotransmission.

Methods

Rats were trained on the three choice serial reaction time task (3-CSRT), an attention test. The impact of systemic or intra-ACC injection of drugs on performance was measured in well-trained rats.

Objective

The present study used a rodent model to compare the inhibition of NMDA and GABA(A) receptors, and GAD activity on attention. We tested the impact of inhibiting these proteins brain wide or in the anterior cingulate cortex (ACC), a prefrontal cortex region critical for attentional processing.

Results

Reducing GABA(A) receptor function within the ACC with the direct antagonist SR95531 (1 or 3 ng/side) or brain wide using systemic injection of the benzodiazepine inverse agonist FG7142 (5 mg/kg) impaired accuracy and increased omissions. Systemic or intra-ACC inhibition of NMDA receptors using MK-801 (at 3 mg/kg or 3 μg, respectively) also impaired performance. Inhibition of GAD with 3-mercaptopropionic acid, even at high doses, had no effect on 3-CSRT accuracy or omissions when administered systemically or within the ACC. Conclusions: These data demonstrate that, while tonic stimulation of NMDA and GABA(A) receptors within the ACC are critical for attentional performance, reduction in GAD activity may have little functional significance and is not indicative of reduced GABA neurotransmission.

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