Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.

  title={Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.},
  author={Raul R. Gainetdinov and William C. Wetsel and Sara R. Jones and Edward D. Levin and Mohamed Jaber and Marc G. Caron},
  volume={283 5400},
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… 

A role for cortical dopamine in the paradoxical calming effects of psychostimulants

Evaluation of PFC dopamine and not norepinephrine or serotonin as a convergent mechanism for the paradoxical psychostimulant effects observe in ADHD therapy is suggested.

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DAT knockout (DAT-KO) mice have an exceptionally large increase in activity in a novel environment, and spatial-cognitive defects can be demonstrated, findings contrary to a simple DA deficiency hypothesis of ADHD.

Dissociations between cognitive and motor effects of psychostimulants and atomoxetine in hyperactive DAT-KO mice

Investigation of the potential involvement of other monoamine systems in the regulation of cognitive functions showed that the norepinephrine transporter blocker atomoxetine restored cognitive performances in DAT-KO mice without affecting hyperactivity, and the nonselective serotonin receptor agonist 5CT had no effect on cognitive functions.

Mice lacking the norepinephrine transporter are supersensitive to psychostimulants

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Adaptations of Presynaptic Dopamine Terminals Induced by Psychostimulant Self-Administration

A great deal of research has focused on investigating neurobiological alterations induced by chronic psychostimulant use in an effort to describe, understand, and treat the pathology of

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The neurobiological bases of attention deficit hyperactivity disorder (ADHD) are explored from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems and recent insights into the previously underestimated role of the NA system in the control of mesocortical DA function are elaborated.

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The origin of ADHD is multifactorial and both the aetiology and pathophysiology of ADHD are as yet incompletely understood, and multiple genetic and environmental factors appear to act together to create a spectrum of neurobiological liability.



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In homozygote mice, dopamine persists at least 100 times longer in the extracellular space, explaining the biochemical basis of the hyperdopaminergic phenotype and demonstrating the critical role of the transporter in regulating neurotransmission.

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