Cerebral Cortex Advance Access published online on November 10, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp236
Opposing Effects of 5,7-DHT Infusions into the Orbitofrontal Cortex and Amygdala on Flexible Responding
1 Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK, 2 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK, 3 Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK, 4 Department of Psychiatry, University of Cambridge, Addenbrookes Hospital, Cambridge, CB2 2QQ, UK
Address correspondence to Angela Roberts. Email: acr4{at}cam.ac.uk.
Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.
Key Words: behavioral inhibition • prepotent response