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Autor Thema: Review: Influence of MPH on Brain Development - Update (Rothenberger et al.)  (Gelesen 3813 mal)


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Thorsten Grund, Konrad Lehmann, Gertraud Teuchert-Noodt (Biolog.Fakultät Uni Bielefeld)
Nathalie Bock, Aribert Rothenberger (Klinik für KiJuPsych, Uni Göttingen)


MPH is an indispensable drug that beautifully fits the pharmacological demands to regulate DA dysfunctions in ADHD. In patients with this disorder, MPH simultaneously compensates a prefrontal DA hypofunction and probably restrains an accumbal DA hyperfunction in the long run. Animal studies suggest that this effect is supported in the PFC by enhancing the maturation of DA fibres [33,34], whereas adaptations of pre- and postsynaptic receptor densities are elicited in the NAc. Both clinical and preclinical studies converge to confirm that in subjects suffering from cognitive-motivational and neural impairments, MPH has long-term beneficial effects in several respects, e.g. by reducing the core symptoms of ADHD as well as the risk for substance abuse [e.g. [102,103,115]. A certain reservation must be deduced from the observation that both the DA innervation and the behavioural function of the amygdala are altered by MPH, making animals more fearful and sensitive to stressful stimuli [33,101]. However, since the behavioural study used normal rats, further investigations are needed to check whether adverse emotional effects are also evoked by MPH in animal models of ADHD.

This latter consideration directly leads us to one of two important caveats concerning the use of MPH: Behavioural studies show that MPH is ineffective in rodents without attentional impairments [82], as far as attention is concerned. In contrast, MPH elicits locomotor sensitization in non-hyperactive rat strains, whereas it has no such effect in SHRs [98]. The assessment of DA fibre densities confirms that these are only improved in previously traumatised animals, but unchanged or possibly even reduced in healthy controls [33,34]. Transformed to a clinical perspective, this might suggest that physicians are possibly dealing with (at least partly) quantitatively and/or qualitatively different responder systems when treating the brains of children with or without ADHD [see also [7,116]]. This perspective is supported by different effects of MPH on neuronal excitability (measured with transcranial magnetic stimulation) in healthy persons compared with ADHD patients [96]. However, as discussed above, there are also partly conflicting data [90-95], making it impossible to arrive at a firm conclusion so far.

Finally, being a psychostimulant, MPH has unfortunately also been discovered by some as a drug of abuse that is intravenously applied. First results on the long-term effect of such abuse in animals has shown equivocal results, with negative effects similar to methamphetamine in low but no effect with high doses of MPH [33,79]. It remains to be checked whether it may even be neurotoxic under such conditions. Nevertheless, the wealth of human and animal information on MPH shows the great value of the drug which has to be handled with care to use it in the right way....