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

@article{Gainetdinov1999RoleOS,
  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},
  journal={Science},
  year={1999},
  volume={283 5400},
  pages={
          397-401
        }
}
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

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

Psychostimulant treatment of hyperactivity and serotonin

  • Psychology, Biology
  • 1999
TLDR
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

TLDR
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

TLDR
In a classical test for antidepressant drugs, the NET-deficient (NET−/−) animals behaved like antidepressant-treated wild-type mice, and were hyper-responsive to locomotor stimulation by cocaine or amphetamine.

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

The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles.

TLDR
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.

[Neurobiology of attention deficit hyperactivity disorder].

TLDR
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.
...

References

SHOWING 1-10 OF 83 REFERENCES

Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter

TLDR
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.

The spectrum of behaviors influenced by serotonin

  • I. Lucki
  • Psychology, Biology
    Biological Psychiatry
  • 1998

Amphetamine: effects on catecholamine systems and behavior.

TLDR
The effects of AMPH in humans have close parallels in animals and at low doses, AMPH increases stereotypic locomotor activity and species-specific stereotypies at higher doses and interferes with intake.

Serotonergic functions in arousal and motor activity

  • M. Geyer
  • Biology, Psychology
    Behavioural Brain Research
  • 1995

HOW AMPHETAMINE ACTS IN MINIMAL BRAIN DYSFUNCTION *

TLDR
Most neuropharmacologists currently consider inhibition of reuptake inactivation and direct synaptic release to be the major mechanisms of amphetamine action in the brain, and amphetamine increases the amount of norepinephrine or dopamine available at synapses for receptor stimulation.

Neural Systems Underlying Arousal and Attention: Implications for Drug Abuse a

TLDR
Evidence in rats with selective neurochemical manipulations tested behaviorally using an analog of an attentional task developed for human subjects indicates that the coeruleo‐cortical noradrenergic system is implicated in divided and selective attention.
...