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
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
Murphy ER, Dalley JW, Laane KF, Cardinal RN, Hellemans KGC, Robbins
Dept of Experimental Psychology, University of Cambridge, Cambridge, UK
Support contributed by: Wellcome Trust and Gates Cambridge Trust