Dopamine in the striatum is known to be important for reversal learning. However, the striatum does not act in isolation and reversal learning is also well-accepted to depend on the orbitofrontal cortex (OFC) and the amygdala. Here we assessed whether dopaminergic drug effects on human striatal BOLD signaling during reversal learning is associated with anatomical connectivity in an orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging (DTI). By using a fiber-based approach, we demonstrate that dopaminergic drug effects on striatal BOLD signal varied as a function of fractional anisotropy (FA) in a pathway connecting the OFC with the amygdala. Moreover, our experimental design allowed us to establish that these white-matter dependent drug effects were mediated via D2 receptors. Thus, white matter dependent effects of the D2 receptor agonist bromocriptine on striatal BOLD signal were abolished by co-administration with the D2 receptor antagonist sulpiride. These data provide fundamental insight into the mechanism of action of dopaminergic drug effects during reversal learning. In addition, they may have important clinical implications by suggesting that white matter integrity can help predict dopaminergic drug effects on brain function, ultimately contributing to individual tailoring of dopaminergic drug treatment strategies in psychiatry.
Keywords: dopamine, striatum, amygdala, OFC, reversal learning, diffusion tensor imaging, bromocriptine, sulpiride
Citation: van Der Schaaf ME, Zwiers MP, van Schouwenburg MR, Geurts DEM, Schellekens AFA, Buitelaar JK, Verkes RJ and Cools R (2013) Dopaminergic drug effects during reversal learning depend on anatomical connections between the orbitofrontal cortex and the amygdala. Front. Neurosci. 7:142. doi: 10.3389/fnins.2013.00142
Received: 29 April 2013; Accepted: 21 July 2013;
Published online: 14 August 2013.
Edited by:Jeff A. Beeler, The University of Chicago, USA
Reviewed by:Kerstin Preuschoff, École Polytechnique Fédérale de Lausanne, Switzerland
Copyright © 2013 van Der Schaaf, Zwiers, van Schouwenburg, Geurts, Schellekens, Buitelaar, Verkes and Cools. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Marieke E. van der Schaaf, Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Kapittelweg 29, PO Box 9101, 6525 EN Nijmegen, Netherlands e-mail: Marieke.firstname.lastname@example.org