Hypothèses biologiques

Parmi les catécholamines*, le système dopaminergique (ou noradrénergique)  revient souvent dans les hypothèses de recherche sur les neurotransmetteurs. La preuve indirecte en proviendrait de l'efficacité de certains médicaments noradrénergiques, comme le méthylphénidate, la dextroamphétamine, possédant chacun un noyau aromatique et des effets directs sur le système sympathique, en particulier cardiovasculaire (tension artérielle, pulsation cardiaque), donc à proprement éviter dans les maladies cardiovasculaires.

* Sous le nom de catécholamines, se présentent trois composés dérivés de la phényléthylamine, tous hydroxylés en position 3 et 4 sur le noyau aromatique. Il s'agit de l’adrénaline, la noradrénaline et la dopamine. L’adrénaline qui a une action hormonale et provient surtout de la glande médullo-surrénale, agit sur les récepteurs Bêta. La noradrénaline, surtout localisé dans l'hypothalamus, est aussi un neurotransmetteur des terminaisons nerveuses sympathiques, récepteurs Alpha 1 & 2, et comme la dopamine, agent transmetteur dans le système nerveux central.

ADHD: increased dopamine receptor availability linked to attention deficit and low neonatal cerebral blood flow.

Lou HC, Rosa P, Pryds O, Karrebaek H, Lunding J, Cumming P, Gjedde A.
Centre of Functionally Integrative Neuroscience and PET Centre, Aarhus University Hospital, Aarhus, Denmark. hclou@inet.uni2.dk

Attention-deficit-hyperactivity disorder (ADHD), while largely thought to be a genetic disorder, has environmental factors that appear to contribute significantly to the aetiopathogenesis of the disorder. One such factor is pretern birth with vulnerable cerebrovascular homeostasis. We hypothesised that cerebral ischaemia at birth could contribute to persistent deficient dopaminergic neurotransmission, which is thought to be the pathophysiological basis of the disorder. We examined dopamine D(2/3) receptor binding with positron emission tomography (PET) using [11C] raclopride as a tracer, and continuous reaction times (RT) with a computerized test of variables (TOVA) in six adolescents (12-14 years of age, one female) who had been examined with cerebral blood flow (CBF) measurements at preterm birth and had a subsequent history of attention deficit. We found that high dopamine receptor availability ('empty receptors') was linked with increased RT and RT variability, supporting the concept of a dopaminergic role in symptomatology. High dopamine receptor availability was predicted by low neonatal CBF, supporting the hypothesis of cerebral ischaemia as a contributing factor in infants susceptible to ADHD.
PMID: 14995087 [PubMed - indexed for MEDLINE]

The dopaminergic system in attention deficit/hyperactivity disorder.

Ohno M.
Department of Pediatrics, Shiga University of Medical Science, Otsu 520-2192, Japan. ohno@belle.shiga-med.ac.jp

Numerous studies have shown the importance of the mesocorticolimbic dopamine system in the pathophysiology of attention deficit/hyperactivity disorder. However, there has been inconsistency in the findings of those studies. Varied and sometimes contradictory interpretation has been made on the basis of similar results. It is, therefore, still unclear whether the dopaminergic system is hypo- or hyperfunctioning in attention deficit/hyperactivity disorder. The majority of the functional brain imaging studies in both clinical and experimental settings support hypofunction of the basal ganglia which receive abundant dopaminergic afferent. The experimental studies, using dopamine-depleted animals, also support the hypodopaminergic hypothesis, whereas recent studies with the dopamine transporter knockout/knockdown mouse suggest hyperdopaminergic function as the underlying abnormality. In this review we attempt to clarify the issues raised by previous neuroimaging and functional neuroimaging studies. Research involving animal models with genetic traits, genetic manipulation or with brain lesions is analysed, concentrating on the significance of the dopaminergic system in the abnormal behavior of attention deficit/hyperactivity disorder. In addition, the functional state of the dopaminergic system is considered through the speculated mechanism of psychostimulant therapy of the disorder. No final conclusions have been reached regarding the pathological, biochemical and physiological mechanisms responsible for various symptoms. Inconsistency in the findings and their interpretations may indicate the heterogeneity of the pathogenesis of this syndrome.
PMID: 12893970 [PubMed - indexed for MEDLINE]

The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder.

Krause KH, Dresel SH, Krause J, la Fougere C, Ackenheil M.
Friedrich-Baur-Institute, Ludwig-Maximilians-University, Ziemssenstr. 1a, D-80336 Munich, Germany. khkrause@yahoo.com

There is evidence that abnormalities within the dopamine system in the brain play a major role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). For instance, dopaminergic psychostimulants, the drugs of first choice in ADHD, interact directly with the dopamine transporter (DAT). Molecular genetic studies suggest involvement of a polymorphism of the DAT gene in ADHD. More recent imaging studies show abnormalities in various brain structures, but particularly in striatal regions. In the current paper we review recent studies in this area. First in vivo measurements of DAT with single photon emission computed tomography (SPECT) in ADHD patients revealed an elevation of striatal DAT density. No differences in DAT density between the left and right side and between putamen and caudate nucleus have been found in [99mTc]TRODAT-1 SPECT of ADHD patients. Patients with ADHD and with a history of nicotine abuse both displayed lower values of DAT density in [99mTc]TRODAT-1 SPECT than non-smokers with ADHD. DAT seem to be elevated in non-smoking ADHD patients suffering from the purely inattentive subtype of ADHD as well as in those with the combined or purely hyperactive/impulsive subtype.
PMID: 14624805 [PubMed - indexed for MEDLINE]