Amphetamine sensitization alters reward processing in the human striatum and amygdala.
- O'Daly OG Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom; Department of Neuroimaging, Centre for Neuroimaging Sciences, the Institute of Psychiatry, King's College London, London, United Kingdom.
- Joyce D Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom.
- Tracy DK Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom; Oxleas NHS Foundation Trust, London, United Kingdom.
- Azim A Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom.
- Stephan KE Laboratory for Social and Neural Systems Research, Department of Economics, University of Zürich, Zürich, Switzerland; Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom.
- Murray RM Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom.
- Shergill SS Cognition, Schizophrenia & Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King's College London, London, United Kingdom; The National Psychosis Unit, South London, and Maudsley NHS Foundation Trust, London, United Kingdom.
- 2014-04-11
Published in:
- PloS one. - 2014
Adult
Amygdala
Anticipation, Psychological
Caudate Nucleus
Central Nervous System Stimulants
Corpus Striatum
Decision Making
Dextroamphetamine
Dopamine
Dopaminergic Neurons
Double-Blind Method
Gambling
Games, Experimental
Humans
Magnetic Resonance Imaging
Male
Motivation
Oxygen
Reaction Time
Reward
Young Adult
English
Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1371/journal.pone.0093955
- PMID 24717936
- Persistent URL
- https://sonar.ch/global/documents/298221
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