Local glutamate receptor antagonism in the rat prefrontal cortex disrupts response inhibition in a visuospatial attentional task

Abstract

Rationale: Converging evidence implicates discrete areas of the rat prefrontal cortex in the modulation of different aspects of attention and executive control. Furthermore, the pharmacology of these behaviours has been relatively well characterised for the monoamine systems in a task of visuospatial attention, but it is not known how glutamate receptor antagonism in discrete regions of the prefrontal cortex affects attentional performance.

Objectives: To investigate the role of N-methyl-D-aspartate (NMDA) receptor antagonism in the prelimbic and infralimbic cortices (within the same animals) on performance of the five-choice serial reaction time task (5CSRTT), which assesses visuospatial attention and response inhibition.

Methods: Following training on the 5CSRTT, rats were implanted with bilateral guide cannulae aimed at the medial prefrontal cortex (mPFC). Rats received micro infusions of the competitive NMDA receptor antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid [(R)-CPP; dissolved in saline to give 10 ng and 50 ng per side] into the prelimbic cortex, then three more infusions (saline, 10 ng and 50 ng per side) into the infralimbic cortex, in a counterbalanced design. They were then tested on a version of the task identical to that used in training.

Results: (R)-CPP microinfusions impaired accuracy and increased omissions across both cortical regions. (R)-CPP microinfusions robustly increased premature responding only when infused into the infralimbic, but not prelimbic, cortex.

Conclusions: These results indicate that NMDA receptor neurotransmission in the infralimbic cortex is necessary for control of impulsive responding on the 5CSRTT. These results suggest a dissociable role for prefronto-cortical glutamatergic systems in response inhibition, which appear to be functionally localised to the ventromedial infralimbic area of the mPFC.