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Cerebral Cortex Advance Access published online on August 22, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn136
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Differential Contributions of Dopamine and Serotonin to Orbitofrontal Cortex Function in the Marmoset

S. C. Walker1,2, T. W. Robbins1,2 and A. C. Roberts2,3

1 Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK, 2 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street CB2 3EB, UK, 3 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK

Address correspondence to Dr Angela Roberts, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Email: acr4{at}cam.ac.uk.

We have shown previously that the inhibitory control functions of the orbitofrontal cortex (OFC) are disrupted by serotonin, but not dopamine depletions. However, both dopamine and serotonin terminals and receptors are present within the OFC and thus the aim of the present study was to determine the differential contributions of these neurotransmitters to orbitofrontal function. OFC and dopamine are involved in the process by which neutral stimuli take on reinforcing properties, by virtue of their prior association with reward, and guide behavior. Thus, we compared the performance of marmosets with dopaminergic or serotoninergic OFC depletions on a test of conditioned reinforcement. To further our understanding of serotonin in behavioral flexibility, the effect of these depletions was also compared on the extinction of a visual discrimination. Monkeys with serotonin depletions of the OFC displayed stimulus-bound responding on both tests of conditioned reinforcement and discrimination extinction suggesting that orbitofrontal serotonin plays a specific role in preventing competing, task irrelevant, salient stimuli from biasing responding. In contrast, monkeys with dopamine depletion were insensitive to conditioned reinforcers and displayed persistent responding in the absence of reward in extinction, a pattern of deficits that may reflect basic deficits in the associative processing of reward.

Key Words: behavioral flexibility • compulsions • conditioned reinforcement • extinction • reward


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