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Program no. 781.11; 2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2004. Online.

Local glutamate receptor antagonism in the rat prefrontal cortex disrupts response inhibition in a spatial attentional task
Murphy ER, Dalley JW, Laane KF, Cardinal RN, Hellemans KGC, Robbins TW
Dept of Experimental Psychology, University of Cambridge, Cambridge, UK

Excitotoxic lesions of discrete regions of the prefrontal cortex (PFC) produce behavioral dissociations on different aspects of five-choice serial reaction time task (5CSRTT) performance. Here we demonstrate reversible, selective effects of discrete regional NMDA receptor antagonism on inhibitory control using intra-PFC infusions. Male Lister Hooded rats were surgically implanted with bilateral cannulae aimed at the mPFC (AP +3.0, L ±0.75, DV 2.2 from dura) following training to stable baseline on the 5CSRTT. Rats received 6 infusions of 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid (R-CPP) (saline, 10 ng/µl, and 50 ng/µl) in a counterbalanced design. The first 3 infusions were aimed at the prelimbic (PRL) cortex, -3.2 from dura. The second 3 infusions were aimed at the infralimbic (IL) cortex, -4.7 from dura. Rats were assessed on baseline performance of the task on days between infusions. The highest dose of 50 ng/µl had no effect on premature responding when infused into the PRL cortex but resulted in a large and significant increase in premature responding following IL cortical infusions (p<0.03). This dose also increased omissions (p<0.02) and decreased accuracy (p<0.01) in both brain regions. The effect on premature responses was not due to hyperactivity, as response and collection latencies were slightly slowed at 50 ng/µl. The effect on premature responding with glutamate receptor antagonism in the IL cortex is consistent with previous lesion evidence, and further supports the unique functional dissociations of areas within the PFC. Inhibition of "impulsive" responding appears to require glutamate receptors in the IL cortex; dysfunction of this system may contribute to the serial disorganization of behavior seen in patients with frontal lobe damage and neuropsychiatric conditions.

Support contributed by: Wellcome Trust and Gates Cambridge Trust