TY - JOUR T1 - Prefrontal and Monoaminergic Contributions to Stop-Signal Task Performance in Rats JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9254 LP - 9263 DO - 10.1523/JNEUROSCI.1543-11.2011 VL - 31 IS - 25 AU - Andrea Bari AU - Adam C. Mar AU - David E. Theobald AU - Sophie A. Elands AU - Kelechi C. N. A. Oganya AU - Dawn M. Eagle AU - Trevor W. Robbins Y1 - 2011/06/22 UR - http://www.jneurosci.org/content/31/25/9254.abstract N2 - Defining the neural and neurochemical substrates of response inhibition is of crucial importance for the study and treatment of pathologies characterized by impulsivity such as attention-deficit/hyperactivity disorder and addiction. The stop-signal task (SST) is one of the most popular paradigms used to study the speed and efficacy of inhibitory processes in humans and other animals. Here we investigated the effect of temporarily inactivating different prefrontal subregions in the rat by means of muscimol microinfusions on SST performance. We found that dorsomedial prefrontal cortical areas are important for inhibiting an already initiated response. We also investigated the possible neural substrates of the selective noradrenaline reuptake inhibitor atomoxetine via its local microinfusion into different subregions of the rat prefrontal cortex. Our results show that both orbitofrontal and dorsal prelimbic cortices mediate the beneficial effects of atomoxetine on SST performance. To assess the neurochemical specificity of these effects, we infused the α2-adrenergic agonist guanfacine and the D1/D2 antagonist α-flupenthixol in dorsal prelimbic cortex to interfere with noradrenergic and dopaminergic neurotransmission, respectively. Guanfacine, which modulates noradrenergic neurotransmission, selectively impaired stopping, whereas blocking dopaminergic receptors by α-flupenthixol infusion prolonged go reaction time only, confirming the important role of noradrenergic neurotransmission in response inhibition. These results show that, similar to humans, distinct networks play important roles during SST performance in the rat and that they are differentially modulated by noradrenergic and dopaminergic neurotransmission. This study advances our understanding of the neuroanatomical and neurochemical determinants of impulsivity, which are relevant for a range of psychiatric disorders. ER -