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Cerebral Cortex Advance Access originally published online on August 18, 2006
Cerebral Cortex 2007 17(6):1444-1453; doi:10.1093/cercor/bhl057
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Dopamine and Noradrenaline Efflux in the Medial Prefrontal Cortex During Serial Reversals and Extinction of Instrumental Goal-Directed Behavior

Jamilja A. J. van der Meulen, Ruud N. J. M. A. Joosten, Jan P. C. de Bruin and Matthijs G. P. Feenstra

Netherlands Institute for Neurosciences, Graduate School of Neurosciences Amsterdam, 1105 AZ Amsterdam, The Netherlands

Address correspondence to Matthijs G.P. Feenstra, Netherlands Institute for Neuroscience, Meibergdreef 33, 1105 AZ Amsterdam ZO, The Netherlands. Email: m.feenstra{at}nin.knaw.nl.

The prefrontal cortex (PFC) of the rat supports cognitive flexibility, the ability to spontaneously adapt goal-directed behavior in response to radically changing situational demands. We have shown previously that transient inactivation of the rat medial PFC (mPFC) impairs initial reversal learning in a spatial 2-lever discrimination task. Given the importance of dopamine (DA) for PFC function, we studied DA (and noradrenaline [NA]) efflux in the mPFC during reversal learning. We observed a higher and more extended increase in DA efflux in rats performing the first reversal compared with controls performing the previously acquired discrimination. The results of an additional experiment suggest that such a difference between the reversal- and control-induced DA increases was absent during a third reversal. During the extinction session, DA efflux did not increase from basal levels. Increases in NA efflux were less than in DA and did not differ between control and any condition. We conclude that prefrontal DA activity is increased during execution of instrumental discrimination tasks and that this increase is amplified during the acquisition of a first, but not of later reversals. These data corroborate our previous findings and indicate that DA is critically involved in this form of cognitive flexibility.

Key Words: cognitive flexibility • dopamine • medial prefrontal cortex • microdialysis • noradrenaline • reversal learning


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