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Science 15 January 1999:
Vol. 283. no. 5400, pp. 397 - 401
DOI: 10.1126/science.283.5400.397
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Reports

Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on Hyperactivity

Raul R. Gainetdinov, William C. Wetsel, Sara R. Jones, Edward D. Levin, Mohamed Jaber, * Marc G. Caron dagger

The mechanism by which psychostimulants act as calming agents in humans with attention-deficit hyperactivity disorder (ADHD) or hyperkinetic disorder is currently unknown. Mice lacking the gene encoding the plasma membrane dopamine transporter (DAT) have elevated dopaminergic tone and are hyperactive. This activity was exacerbated by exposure to a novel environment. Additionally, these mice were impaired in spatial cognitive function, and they showed a decrease in locomotion in response to psychostimulants. This paradoxical calming effect of psychostimulants depended on serotonergic neurotransmission. The parallels between the DAT knockout mice and individuals with ADHD suggest that common mechanisms may underlie some of their behaviors and responses to psychostimulants.

R. R. Gainetdinov, S. R. Jones, M. Jaber, M. G. Caron, Howard Hughes Medical Institute Laboratories, Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710, USA. W. C. Wetsel, Departments of Psychiatry and Medicine (Endocrinology), Duke University Medical Center, Durham, NC 27710, USA. E. D. Levin, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
*   Present address: CNRS UMR5541, University of Bordeaux II Victor Segalen, 146 Rue Leo Saignat, 33076 Bordeaux Cedex, France.

dagger    To whom correspondence should be addressed. E-mail: caron002{at}mc.duke.edu

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