Repository logo
 

Fractionating Blunted Reward Processing Characteristic of Anhedonia by Over-Activating Primate Subgenual Anterior Cingulate Cortex.

Published version
Peer-reviewed

Loading...
Thumbnail Image

Type

Article

Change log

Authors

Gaskin, Philip LR 
Sawiak, Stephen J 
Fryer, Tim D 
Hong, Young T 

Abstract

Anhedonia is a core symptom of depression, but the underlying neurobiological mechanisms are unknown. Correlative neuroimaging studies implicate dysfunction within ventromedial prefrontal cortex, but the causal roles of specific subregions remain unidentified. We addressed these issues by combining intracerebral microinfusions with cardiovascular and behavioral monitoring in marmoset monkeys to show that over-activation of primate subgenual anterior cingulate cortex (sgACC, area 25) blunts appetitive anticipatory, but not consummatory, arousal, whereas manipulations of adjacent perigenual ACC (pgACC, area 32) have no effect. sgACC/25 over-activation also reduces the willingness to work for reward. 18F-FDG PET imaging reveals over-activation induced metabolic changes in circuits involved in reward processing and interoception. Ketamine treatment ameliorates the blunted anticipatory arousal and reverses associated metabolic changes. These results demonstrate a causal role for primate sgACC/25 over-activity in selective aspects of impaired reward processing translationally relevant to anhedonia, and ketamine's modulation of an affective network to exert its action.

Description

Keywords

PET imaging, anhedonia, anterior cingulate, area 25, depression, ketamine, marmoset, motivation, reward, subgenual, Anhedonia, Animals, Blood Pressure, Callithrix, Citalopram, Conditioning, Classical, Discrimination, Psychological, Disease Models, Animal, Excitatory Amino Acid Antagonists, Female, Fluorodeoxyglucose F18, Food Preferences, Gyrus Cinguli, Humans, Ketamine, Locomotion, Male, Proto-Oncogene Proteins c-fos, Reward, Selective Serotonin Reuptake Inhibitors, Stress, Psychological, Sucrose

Journal Title

Neuron

Conference Name

Journal ISSN

0896-6273
1097-4199

Volume Title

101

Publisher

Elsevier BV
Sponsorship
MRC (1648124)
Medical Research Council (G1100307)
Wellcome Trust (108089/Z/15/Z)