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Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine

Nature volume 261, pages 153–155 (1976)Cite this article

Abstract

THE clinical syndrome of minimal brain dysfunction (MBD) in children is characterised by hyperactive motor behaviour, decreased attention span, impulsiveness and a variety of cognitive and perceptual problems. A striking feature of the disorder is the unusual response to stimulant medication. Thus, administration of amphetamine to children with MBD results in a sharp decrease in motor activity. Since the usual pharmacological response to amphetamine is an increase in motor activity, this response has been termed “paradoxical”1. We have described an experimental model in the developing rat that is strikingly similar to the clinical syndrome of MBD found in children2. Rat pups treated with 6-hydroxydopamine (6-OHDA) at 5 d of age develop increased motor activity and demonstrate cognitive difficulties in shuttle-box learning between 2 and 4 weeks of age. We now report that administration of (+)-amphetamine reduces the hyperactivity in 6-OHDA-treated rat pups, an effect paralleling the paradoxical response to this agent in children with MBD. The similarity of many of the cardinal features of MBD in an experimental model produced by depletion of brain dopamine in developing rats supports the belief that brain monoamines may be involved in the pathogenesis of this disorder.

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Authors and Affiliations

  1. Section of Pediatric Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510

    BENNETT A. SHAYWITZ, JEFFREY H. KLOPPER, ROBERT D. YAGER & JUDITH W. GORDON

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  1. BENNETT A. SHAYWITZ
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  2. JEFFREY H. KLOPPER
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  3. ROBERT D. YAGER
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  4. JUDITH W. GORDON
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SHAYWITZ, B., KLOPPER, J., YAGER, R. et al. Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine. Nature 261, 153–155 (1976). https://doi.org/10.1038/261153a0

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