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Cerebral Cortex Advance Access published online on July 22, 2009
Cerebral Cortex, doi:10.1093/cercor/bhp139
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Memory Encoding and Dopamine in the Aging Brain: A Psychopharmacological Neuroimaging Study

Alexa M. Morcom1,2, Edward T. Bullmore3,4,5, Felicia A. Huppert6, Belinda Lennox4, Asha Praseedom4, Helen Linnington7 and Paul C. Fletcher4

1 Department of Psychology and Centre for Cognitive and Neural Systems, 2 University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, EH8 9JZ Scotland, UK, 3 Behavioural and Clinical Neurosciences Institute, 4 Department of Psychiatry, University of Cambridge, CB2 3EB Cambridge, UK, 5 Clinical Unit Cambridge, Clinical Pharmacology & Discovery Medicine, GlaxoSmithKline, CB2 2QQ Cambridge, UK, 6 Well-Being Institute, Department of Psychiatry, Cambridge University, CB2 2QQ Cambridge, UK, 7 The Longley Centre, Sheffield Health and Social Care NHS Foundation Trust, S5 7JT Sheffield, UK

Address correspondence to Dr Alexa Morcom, Department of Psychology and Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. Email: alexa.morcom{at}ed.ac.uk.

Normal aging brings with it changes in dopaminergic and memory functions. However, little is known about how these 2 changes are related. In this study, we identify a link between dopamine, episodic memory networks, and aging, using pharmacological functional magnetic resonance imaging. Young and older adults received a D2-like agonist (Bromocriptine, 1.25 mg), a D2-like antagonist (Sulpiride, 400 mg), and Placebo, in a double-blind crossover procedure. We observed group differences, during memory encoding, in medial temporal, frontal, and striatal regions and moreover, these regions were differentially sensitive across groups to dopaminergic perturbation. These findings suggest that brain systems underlying memory show age-related changes and that dopaminergic function may be key in understanding these changes. That these changes have behavioral consequences was suggested by the observation that drug modulations were most pronounced in older subjects with poorer recognition memory. Our findings provide direct evidence linking ageing, memory, and dopaminergic change.

Key Words: aging • dopamine • encoding • fMRI • memory


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