The first answers on the functioning of psychostimulants that are used in the treatment of some childhood psychiatric pathologies come from studies conducted on laboratory animals .
For more than 70 years, psychostimulants used to treat hyperactivity in children have been a real enigma for clinicians and researchers, also arousing controversy in the medical world.
The controversy arises from an apparently obvious question: how is it possible that psychostimulants calm rather than exacerbate the symptoms of hyperactivity
In fact these drugs that include cocaine and derivatives from amphetamines, phenmetrazine, methylamphetamine, methylphenidateand diethylpropion, are psychostimulants that normally have an activating action on dopamine receptors, inhibit their absorption in some areas and cause a release in others, resulting in an increase in activity and contributing to the addictive effect.
The drug used in the treatment of attention deficit hyperactivity disorder(ADHD, from the English acronym) and above all methylphenidate, a stimulant of the central nervous system not very powerful with more pronounced effects on mental than on motor activities. The pharmacological properties are the same as those of amphetamines with which it also shares the risk of abuse. It is also effective in the treatment of narcolepsy as well as in dysfunctions that cause disturbances in attention with hyperactivity (ADHD) (Goodman & Gilman, 1996).
The clinical evidence that these drugs work in ADHD is the basis of the catecholaminergic theory in which the neurotransmitters dopamine and noradrenaline are involved. In this disorder there would be a fronto-limbic dysfunction with a defective inhibitory control of the cortex by the limbic system, and which would be at the origin of many of the symptoms of the disease and stimulants such as methamphetamine, dexamphetamine and methylphenidate improve symptoms in 70% of cases. (Leonard, 2003).

A study conducted on laboratory animals reveals why a psychostimulating drug works in hyperactivity, paving the way for the understanding of this pathology in humans and the possible development of new therapeutic routes.
By injecting methylphenidatedirectly in dopamine D4 receptors in the reticular nuclei of the thalamus and in the reticulated substantia nigra of rats , the researchers observed a reduction in motor activity in these areas. In patients with ADHD there is a defect in this gene that controls dopamine D4 receptors, although the relationship between the genetic defect and disease expression is unclear.
The choice of these areas, says David Erlij in an interview with Medscape (2012), is due precisely to the fact that the role of dopamine in these areas had been neglected.
With this discovery, the paradox of the effect of stimulants is finally resolved and a new path opens up for the study of new drugs useful in the treatment of ADHD.

Erlij D, Acosta-Garcia J, Rojas-Marquez M, Gonzalez-Hernandez B, Escartin-Perez E, Aceves J, Floran B. Dopamine D4 receptor stimulation in GABAergic projections of the globus pallidus to the reticular thalamic nucleus and the substantia nigra reticulata of the rat decreases locomotor activity. Neuropharmacology, 2012; 62: 1111-1118.
Goodman & Gilman’s. The pharmacological basis of therapeutics. Ninth Edition. McGraw-Hill, 1998.
Leonard BE. Fundamentals of psychopharmacology. Third Edition. Wiley, 2003.
Mistery of psychostimulant paradox solved. Medscape, 2012.

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