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Selective Effects of Acute Serotonin and Catecholamine Depletion on Memory in Healthy Women

Neuropsychopharmacology Laboratory, Brain Sciences Institute, Swinburne University of Technology, Melbourne Australia

James S. Olver

University of Melbourne, Department of Psychiatry, Austin and Repatriation Medical Centre, Melbourne Australiam

Trevor R. Norman

University of Melbourne, Department of Psychiatry, Austin and Repatriation Medical Centre, Melbourne Australia

Graham D. Burrows

University of Melbourne, Department of Psychiatry, Austin and Repatriation Medical Centre, Melbourne Australia

Keith A. Wesnes

Cognitive Drug Research Ltd, CDR House, Reading UK

Pradeep J. Nathan

Neuropsychopharmacology Laboratory, Brain Sciences Institute, Swinburne University of Technology, Melbourne Australia pnathan{at}bsi.swin.edu.au

There is converging evidence that brain serotonin and dopamine may selectively modulate learning and memory in humans. However, this has not been directly demonstrated. In the current study, we used the method of amino acid precursor depletion to explore the effects of low serotonin and catecholamine function on memory in healthy female volunteers. Participants completed three experimental sessions: (i) tryptophan depletion (TD to lower 5-HT); (ii) tyrosine and phenylalanine depletion (TPD to lower catecholamines); and (iii) a balanced control condition (Bal). All testing was conducted in a double-blind, placebo-controlled, crossover design. Cognitive and mood assessments were performed at baseline and 5 h after ingesting the amino acid mixture. Consistent with previous studies, TD impaired declarative memory consolidation on a structured word-learning task, while TPD, acting to lower brain dopamine availability, impaired spatial working memory. No secondary deficits were observed on measures of attention, short-term memory or subjective mood state. These findings suggest that low brain serotonin versus dopamine selectively impairs memory performance in humans. This may shed light on the role of these neurotransmitters in disorders that are characterized by significant memory impairment.

Key Words: amino acid • cognition • consolidation • dopamine • learning • serotonin • tryptophan depletion • tyrosine depletion • working memory

Journal of Psychopharmacology, Vol. 18, No. 1, 32-40 (2004)
DOI: 10.1177/0269881104040225


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